Pharmaceutical compositions, methods of making pharmaceutical compositions, and kits comprising 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}4-chlorophenyl dihydrogen phosphate

ABSTRACT

Provided are novel formulations of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate as described below and uses thereof.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/035,006 filed May 6, 2016, which is a National Stage Entry under 35U.S.C. § 371 of International Application No. PCT/US2014/064441 filedNov. 6, 2014, which claims priority to U.S. Provisional Application No.61/900,878 filed Nov. 6, 2013, U.S. Provisional Application No.61/900,919 filed Nov. 6, 2013, and U.S. Provisional Application No.61/900,946 filed Nov. 6, 2013, the contents of each of which areincorporated herein by reference.

TECHNICAL FIELD

Provided are novel formulations of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate as described below and uses thereof.

BACKGROUND

Aquaporins are cell membrane proteins that act as molecular waterchannels to mediate the flow of water in and out of the cells. Whilethere is some degree of passive diffusion or osmosis of water acrosscell membranes, the rapid and selective transport of water in and out ofcells involves aquaporins. These water channels selectively conductwater molecules in and out of the cell, while blocking the passage ofions and other solutes, thereby preserving the membrane potential of thecell. Aquaporins are found in virtually all life forms, from bacteria toplants to animals. In humans, they are found in cells throughout thebody.

Aquaporin inhibitors, e.g., inhibitors of AQP4 and/or AQP2, may be ofutility in the treatment or control of diseases of water imbalance, forexample edema (particularly edema of the brain and spinal cord),hyponatremia, and excess fluid retention, as well as diseases such asepilepsy, retinal ischemia and other diseases of the eye, myocardialischemia, myocardial ischemia/reperfusion injury, myocardial infarction,myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitisoptica, as well as migraines.

Prior to Applicants' filings, there have been no known specific,validated inhibitors of aquaporins, for example AQP4 or AQP2. Certainantiepileptic or sulfonamide drugs (e.g., acetylsulfanilamide,acetazolamide, 6-ethoxy-benzothiazole-2-sulfonamide, topiramate,zonisamide, phenytoin, lamotrigine, and sumatriptan) were at one pointreported to be possible inhibitors of AQP4, but this later proved to beincorrect. Yang et al., Bioorganic and Medicinal Chemstry, 2008, 16,7489-7493. No direct inhibitors of AQP2 have been reported.

Thus, there is a need for compounds that selectively inhibit aquaporins.In addition, there is a need for formulations that may be used todeliver compounds that selectively inhibit aquaporins and may beadministered easily to patients.

BRIEF SUMMARY

Provided are pharmaceutical compositions comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate (Formula I).

and uses thereof.

Also provided are kits comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate.

Also provided is a method of treating or controlling a disease orcondition mediated by an aquaporin, e.g., diseases or conditions ofwater imbalance and other diseases, for example,

-   -   edema of the brain or spinal cord, e.g., cerebral edema, e.g.        cerebral edema consequent to head trauma, ischemic stroke,        glioma, meningitis, acute mountain sickness, epileptic seizure,        infection, metabolic disorder, hypoxia (including general        systemic hypoxia and hypoxia due to cardiac arrest), water        intoxication, hepatic failure, hepatic encephalopathy, diabetic        ketoacidosis, abscess, eclampsia, Creutzfeldt-Jakob disease,        lupus cerebritis, cardiac arrest, microgravity and/or radiation        exposure, or an invasive central nervous system procedure, e.g.,        neurosurgery, endovascular clot removal, spinal tap, aneurysm        repair, or deep brain stimulation or, e.g., spinal cord edema        consequent to spinal cord trauma, e.g., spinal cord compression;        or    -   optic nerve edema, e.g., optic nerve edema consequent to        microgravity and/or radiation exposure; or    -   retinal edema; or    -   pulmonary edema; or    -   hyponatremia or excessive fluid retention, e.g., consequent to        heart failure (HF), liver cirrhosis, nephrotic disorder,        syndrome of inappropriate antidiuretic hormone secretion        (SIADH), or infertility treatment; or    -   ovarian hyperstimulation syndrome; or    -   epilepsy, retinal ischemia or other diseases of the eye        associated with abnormalities in intraocular pressure and/or        tissue hydration, myocardial ischemia, myocardial        ischemia/reperfusion injury, myocardial infarction, myocardial        hypoxia, congestive heart failure, sepsis, neuromyelitis optica,        or glioblastoma; or    -   fibromyalgia; or    -   multiple sclerosis; or    -   migraines,        comprising administering to a patient in need thereof a        pharmaceutical composition comprising a therapeutically        effective amount of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate.

Further areas of applicability of the present disclosure will becomeapparent from the detailed description provided hereinafter. It shouldbe understood that the detailed description and specific examples, whileindicating the preferred embodiment of the disclosure, are intended forpurposes of illustration only and are not intended to limit the scope ofthe disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts percent survival curves for the water toxicity mousemodel using 0.76 mg/kgN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (Compound1).

FIG. 2 depicts inhibition of cerebral edema formation byN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide(Compound 1) in the mouse water toxicity model by MRI brain volumeanalysis, with n=14 mice/treatment. A time course of edema formation isshown comparing no drug vs.N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide(Compound 1) at 0.76 mg/kg. The first time point at 5.67 min coincideswith the scan slice at the middle of the brain during the firstpost-injection scan. Other time points are placed in a similar manner.The data is fitted to a single exponential equation:V/V ₀ =V _(i) +dVmax(1−e ^((−kt)));where V/V₀=relative brain volume, V_(i)=initial relative brain volume,dV_(max)=maximum change in relative brain volume, k=first order rateconstant (min), and t=time in minutes.

FIG. 3 depicts the calcein fluorescence end-point assay used for highthroughput screening.

FIG. 4 depicts hit validation using the Cell Bursting Aquaporin Assay;inset shows the structure of5-chloro-N-(3,5-dichlorophenyl)-2-hydroxybenzamide (Compound 3).

FIG. 5 depicts reduction in intracranial pressure (ICP) in the mousewater toxicity model withN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide(Compound 1) at 0.76 mg/kg.

FIG. 6 depicts plasma and serum levels ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide(Compound 1) converted from2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl phosphatebis ethanolamine salt.

FIG. 7 depicts mouse middle cerebral artery occlusion (MCAo) model ofischemic stroke.

FIG. 8 depicts relative change in hemispheric brain volume in the mousemiddle cerebral artery occlusion (MCAo) model.

FIG. 9 depicts neurological outcome following MCAo in mice treated withsaline (no drug, •) or2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatedisodium salt (∘) (Compound 5).

FIG. 10 depicts plasma and serum levels ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide(Compound 1) converted from a solution of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate and Tris-Base.

DETAILED DESCRIPTION

The following description of the preferred embodiments is merelyexemplary in nature and is in no way intended to limit the presentdisclosure, its application, or uses.

As used herein, “therapeutically effective amount” refers to an amounteffective, when administered to a human or non-human patient, to providea therapeutic benefit such as amelioration of symptoms, slowing ofdisease progression, or prevention of disease. The specific dose ofsubstance administered to obtain a therapeutic benefit will, of course,be determined by the particular circumstances surrounding the case,including, for example, the specific substance administered, the routeof administration, the condition being treated, and the individual beingtreated.

As used herein, “sodium phosphate” refers to sodium dihydrogen phosphate(NaH₂PO₄), disodium hydrogen phosphate (Na₂HPO₄), and trisodiumphosphate (Na₃PO₄).

As used herein, “potassium phosphate” refers to potassium dihydrogenphosphate (KH₂PO₄), dipotassium hydrogen phosphate (K₂HPO₄), andtripotassium phosphate (K₃PO₄).

As used herein, “bolus” refers to administration of a therapeutic agentin a single injection that lasts for a relatively short period of time,e.g., about 60 minutes or less, about 30 minutes or less, about 20minutes or less, about 10 minutes or less, about 5 minutes or less,e.g., about 3 minutes or less. A bolus may rapidly deliver atherapeutically effective amount of a therapeutic agent to the blood.

As used herein, “patient” includes human or non-human (i.e., animal)patient. In a particular embodiment, the invention encompasses bothhuman and nonhuman. In another embodiment, the invention encompassesnonhuman. In another embodiment, the term encompasses human.

As used herein, “fairly rapid” with respect to onset of action meansthat the time it takes after a compound is administered for a responseto be observed is 30 minutes or less, for example 20 minutes or less,for example 15 minutes or less, for example 10 minutes or less, forexample 5 minutes or less, for example 1 minute or less.

As used herein, “alkyl” is a saturated hydrocarbon moiety, preferablyhaving one to six carbon atoms, preferably having one to four carbonatoms, which may be linear or branched. A “C₁₋₄-alkyl” is an alkylhaving one to four carbon atoms.

As used herein “alkylene” is a saturated hydrocarbon moiety, preferablyhaving one to six carbon atoms, preferably having one to four carbonatoms, which may be linear or branched and which has two points ofattachment. A C₁₋₄-alkylene is an alkylene having from one to fourcarbon atoms. For example, C₁-alkylene is methylene (—CH₂—).

As used herein, “alkoxy” is an alkyl ether radical, alkyl-O—, whereinthe term alkyl is as defined above. A “C₁₋₄-alkoxy” is an alkoxy havingone to four carbon atoms.

As used herein, “aryl” is a mono or polycyclic (e.g., bicyclic) aromatichydrocarbon, preferably phenyl, which may be optionally substituted,e.g., optionally substituted with one or more groups independentlyselected from C₁₋₆ alkyl (e.g., methyl), halogen (e.g., Cl or F),C₁₋₆-haloalkyl (e.g., trifluoromethyl), hydroxy, and carboxy. In someembodiments, aryl, in addition to being substituted with the groupsdisclosed herein, is further substituted with an aryl or a heteroaryl toform, e.g., biphenyl or pyridylphenyl.

As used herein, “heteroaryl” is an mono or polycyclic (e.g., bicyclic)aromatic moiety wherein one or more of the atoms making up the aromaticring is sulfur or nitrogen rather than carbon, e.g., pyridyl orthiadiazolyl, which may be optionally substituted, e.g., optionallysubstituted with one or more groups independently selected from C₁₋₆alkyl (e.g., methyl), halogen (e.g., Cl or F), C₁₋₆-haloalkyl (e.g.,trifluoromethyl), hydroxy, and carboxy.

As used herein, “hydroxy” is —OH.

As used herein, “carboxy” is —COOH.

As used herein, “halogen” as used herein is F, Cl, Br, or I.

As used herein, “haloalkyl” is a saturated hydrocarbon moiety,preferably having one to six carbon atoms, preferably having one to fourcarbon atoms, which may be linear or branched, and is mono-, di- ortri-substituted with halogen. For di- or tri-substituted haloalkyl, thehalogens may be the same (e.g., dichloromethyl) or different (e.g.,chlorofluoromethyl).

Expression of Aquaporin-4 (AQP4) is upregulated in animal models oftrauma, stroke and water intoxication, as well as around human malignantbrain tumors. Aquaporin-4 (AQP4) has been shown to play a critical rolein the development of cerebral and spinal cord edema. AQP4 provides theprimary route for water movement across the blood-brain barrier (BBB)and glia limitans. AQP4 knockout mice, without the APQ4 gene, haveimproved survival compared to wild-type mice in models of ischemicstroke, water toxicity, bacterial meningitis, and spinal cordcompression.

Cerebral edema (CE) may be generally divided into 2 major categories:vasogenic and cytotoxic. Vasogenic cerebral edema may occur when abreach in the BBB allows water and solutes to diffuse into the brain. Ithas been reported that AQP4-null mice have increased brain edema in amodel of subarachnoid hemorrhage, suggesting that AQP4 may be requiredfor the clearance of water collected in intercellular space. Incontrast, cytotoxic cerebral edema may be initiated by ischemia whichmay result in reduced plasma osmolality rather than a disrupted BBB.Ischemia may lead to a drop in ATP levels, which is thought to slow theNa—K ATPase pump resulting in an uptake of Na⁺ and Cl⁻ through leakagepathways. The net effect may be a cellular osmotic imbalance, drawingH₂O into cells—astrocytes more so than neurons—and leading to increasedintracranial pressure (ICP). Mouse models for ischemic stroke, watertoxicity, bacterial meningitis, and spinal-cord compression fall intothis category. In these models, AQP4-null mice have been reported tohave reduced CE pointing to AQP4 as the central pathway for watermovement into the brain during the formation of cytotoxic CE. However,cytotoxic and vasogenic edema are not sharply divided categories; aninjury that initially causes cytotoxic edema may be followed later,e.g., within the next hours to days, by vasogenic edema. This maysuggest different treatments for cerebral edema at different times.

AQP4 inhibitors may be of further utility for certain ailments wherecontrol of AQP4-medited water movement may augment neuroexcitation (byalteration of neuronal potassium homeostasis) and prove beneficial byreducing neuronal excitation, for example ailments such as fibromyalgia,multiple sclerosis, migraines and seizures (in particular but notlimited to seizures associated with epilepsy).

Aquaporin-2 (AQP2) is the primary route of water movement at thecollecting duct in the kidney. Blocking this water channel would lowerwater reabsorption without incurring electrolyte imbalances orinterfering with vasopressin receptor-mediated signaling. Evidence thatan AQP2 blocker would not produce electrolyte imbalances, and instead bean effective treatment for hyponatremia, comes from patients withdiabetes insipidus who lack functional AQP2. They exhibit chronicaquaresis but—if normal hydration is maintained—do not demonstrate anyother consequence of their long-term loss of AQP2 function.

2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is a prodrug ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (Compound1, shown below).

Certain uses of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate and ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide aredescribed in International Patent Application No. PCT/US2013/040194,which is incorporated herein by reference in entirety.

In stroke or other severely debilitating diseases or conditions, forexample where the patient may be unconscious or unable to swallow, an IVinfusion or IV bolus may be preferred. In addition, when a patient hassuffered a stroke, or traumatic brain or spinal cord injury, rapidachievement of therapeutically effective amounts of a therapeutic agent,may be important to a successful therapeutic outcome. In the acute caresettings in the hospital, particularly for stroke, traumatic braininjury, and myocardial infarction, best practices are to administerdrugs via IV. However, a therapeutic agent with only a limitedsolubility in water and/or physiological media and/or limited stability,may make parenteral administration, e.g., intravenous, intramuscular,intraperitoneal, subcutaneous, epidural, sublingual, or intracerebral,of the therapeutic agent challenging. WhileN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide is anaquaporin inhibitor, its solubility in water is 3.8 μg/ml. Alanine anddi-alanine prodrugs ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide areinsoluble in water and pH 7.4 water (Example 16). A prodrug salt form ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide does showimproved solubility—specifically, the solubility of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatedisodium salt in water is 1 mg/ml. However, prodrug salt forms ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide mayrevert to N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamideeven in the solid state. For instance,2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl hydrogenphosphate mono sodium salt (“mono sodium salt”),2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl phosphatebis sodium salt (“bis sodium salt”), and2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl phosphatebis ethanolamine salt (“bis ethanolamine salt”) show hydrolysis in thesolid state at about 1% per day. Thus, stable pharmaceuticalcompositions which may allow rapid achievement of therapeuticallyeffective amounts ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide areneeded.

Accordingly, in one embodiment, provided are novel formulations of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate which may allow rapid achievement of therapeutically effectiveamounts ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide.

In one embodiment, provided is a pharmaceutical composition (CompositionI) comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate (Formula I) and a pharmaceutically acceptable excipient.

Further provided is Composition I as follows:

-   -   1.1 Composition I wherein the composition comprises 0.1 or 0.25        mg to 2.0 g of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate, e.g., from about 0.1 or 0.25 mg to 75 or        600 mg, e.g., from about 0.1 or 0.25 or 1 or 2 or 5 or 10 or 15        or 20 mg to 50, 75, 100, 125, 150, 200, 300, 350, 400, 500, or        600 mg, or 1 g, 1.5 g, or 2.0 g, e.g., from about 5 to 50, 75,        100, 125, 150, 200, 300, 350, 400, 500, or 600 mg, or 1 g, 1.5        g, or 2 g, e.g., from about 5 to 500 mg, e.g., from about 5 to        300 or 350 mg, e.g., from about 5 to 200 mg, e.g., from about 25        to 500 mg, e.g., from about 25 to 300 or 350 mg, e.g., from        about 25 to 200 mg, e.g., from about 15, 20, 30, 35, 50, or 100        to 150, 200, 300, 350, 400, 450, 500, 550, or 600 mg, e.g., from        about 0.5 or 1 mg to 50 mg, e.g., from about 0.5 or 1 mg to 20        mg, e.g., from about 0.5 or 1 mg to 10 mg, e.g., from about 1 or        2 or 5 mg to 10 or 20 mg, e.g., from about 1 or 2 or 3 or 4 to 5        mg, e.g., about 35 mg, e.g., about 350 mg, or wherein the        composition comprises        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate in an amount sufficient to provide        -   0.1 or 0.25 mg to 2.0 g of            N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,            e.g., in an amount sufficient to provide from about 0.1 or            0.25 mg to 75 or 600 mg, e.g., from about 0.1 or 0.25 or 1            or 2 or 5 or 10 or 15 or 20 mg to 50, 75, 100, 125, 150,            200, 300, 350, 400, 500, or 600 mg, or 1 g, 1.5 g, or 2.0 g,            e.g., from about 5 to 50, 75, 100, 125, 150, 200, 300, 350,            400, 500, or 600 mg, or 1 g, 1.5 g, or 2 g, e.g., from about            5 to 500 mg, e.g., from about 5 to 300 or 350 mg, e.g., from            about 5 to 200 mg, e.g., from about 25 to 500 mg, e.g., from            about 25 to 300 or 350 mg, e.g., from about 25 to 200 mg,            e.g., from about 15, 20, 30, 35, 50, or 100 to 150, 200,            300, 350, 400, 450, 500, 550, or 600 mg, e.g., from about            0.5 or 1 mg to 50 mg, e.g., from about 0.5 or 1 mg to 20 mg,            e.g., from about 0.5 or 1 mg to 10 mg, e.g., from about 1 or            2 or 5 mg to 10 or 20 mg, e.g., from about 1 or 2 or 3 or 4            to 5 mg, e.g., about 35 mg, e.g., about 350 mg.    -   1.2 Composition I wherein the composition comprises        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate in an amount sufficient to provide a dose        of 0.01 or 0.1 or 0.5 mg/kg to 1 or 5 or 10 or 15 mg/kg of        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        e.g., a dose of about 0.05 to 1 or 5 mg/kg, e.g., a dose of        about 0.05 to 0.1, 0.2, 0.3, 0.4, 0.5, 1, 5, 10 or 20 mg/kg,        e.g., a dose of about 0.5 to 1, 2, 3, 4, 5 or 10 or 20 mg/kg,        e.g, a dose of about 1 to 2, 3, 4, 5, 10, 20 or 50 mg/kg.    -   1.3 Composition 1, 1.1, or 1.2 wherein the pharmaceutically        acceptable excipient comprises one or more bases, e.g., a base        wherein upon dissolution of the composition in a solvent, e.g.,        an aqueous solution, the composition has a pH between 7, 7.5, or        8 and 10.5, e.g., between about 7, 7.5, or 8 and 9.5, e.g.,        between about 7 or 7.5 and 8, e.g., between about 7.5 and 8.5,        e.g., about 7.5, e.g., about 8.5, e.g., between about 8 and 8.5,        e.g., about 8.2, e.g., a base wherein a conjugate acid of the        base has a pKa between 6, 7, 8, 9, or 10 and 11, e.g., between        about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9, e.g.,        between about 8 and 9, e.g., wherein the one or more bases are        one or more of:        -   a) a C₁₋₈-alkyl mono-, di-, or tri-carboxylic acid salt,            e.g., a citrate salt, e.g, a metal citrate salt (e.g., an            alkali and/or alkaline citrate salt, e.g., an alkali citrate            salt, e.g., sodium citrate and/or potassium citrate), e.g.,            a tartrate salt (e.g., a metal tartrate salt, an alkali            tartrate, e.g., sodium tartrate), e.g., a succinate salt            (e.g., a metal succinate salt, e.g., an alkali succinate,            e.g., disodium succinate), and/or e.g., a lactate salt            (e.g., a metal lactate salt, e.g., an alkali lactate, e.g.,            sodium lactate),        -   b) a phosphate salt, e.g., a metal phosphate salt (e.g., an            alkali and/or alkaline phosphate salt, e.g., an alkali            phosphate salt, e.g., sodium phosphate (e.g., NaH₂PO₄ and/or            Na₂HPO₄) and/or potassium phosphate (e.g., KH₂PO₄ and/or            K₂HPO₄)),        -   c) an amine and/or a salt thereof (e.g., morpholine,            piperazine, benethamine, benzathine, trimethylglycine,            chloroprocaine, hydrabamine, an amino acid (e.g., arginine            and/or lysine), a mono- and/or poly-hydroxyalkylamine,            and/or a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,            [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each R⁸ is            independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,            e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene            (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—,            e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is            —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,            5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known            as tris base) and/or a salt thereof (e.g.,            tris(hydroxymethyl)aminomethane acetate (also known as tris            acetate), meglumine, dimethylethanolamine, diethylamine,            diethylethanolamine, and/or diethanolamine), e.g., any of            the preceding wherein a conjugate acid of the amine and/or            salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,            e.g., between about 6, 7, 8, or 9 and 10, e.g., between            about 7 and 9, e.g., between about 8 and 9,        -   d) a metal chloride salt (e.g., zinc chloride),        -   e) an acetate salt, e.g., a metal acetate salt (e.g., an            alkali and/or alkaline acetate salt, e.g., an alkali acetate            salt, e.g., sodium acetate and/or potassium acetate),        -   f) a hydroxide and/or alkoxide salt, e.g., a metal hydroxide            and/or metal alkoxide salt (e.g., a quarternary ammonium            hydroxide, e.g., ammonium hydroxide and/or choline            hydroxide, lithium hydroxide, aluminum hydroxide, e.g., an            alkali and/or alkaline hydroxide salt, e.g., sodium            hydroxide, potassium hydroxide, calcium hydroxide, magnesium            hydroxide, and/or magnesium ethoxide, e.g., sodium            hydroxide), and/or        -   g) a carbonate and/or bicarbonate salt, e.g., a metal            carbonate and/or metal bicarbonate salt (e.g., an alkali            and/or alkaline carbonate salt, e.g., an alkali and/or            alkaline bicarbonate salt, e.g., sodium bicarbonate),        -   h) a borate salt, e.g., a metal borate salt (e.g., an alkali            borate salt, e.g., sodium borate),    -    e.g., one or more of sodium citrate, Na₂HPO₄,        tris(hydroxymethyl)aminomethane, and a        tris(hydroxymethyl)aminomethane salt (e.g., tris acetate), e.g.,        one or more of sodium citrate, Na₂HPO₄, and        tris(hydroxymethyl)aminomethane, e.g., one or more of sodium        citrate and Na₂HPO₄, e.g., Na₂HPO₄, e.g.,        tris(hydroxymethyl)aminomethane.    -   1.4 Composition I, 1.1, or 1.2 wherein the pharmaceutically        acceptable excipient comprises one or more bases, e.g., a base        wherein upon dissolution of the composition in an aqueous        solution the composition has a pH between 7, 7.5, or 8 and 10.5,        e.g., between about 7, 7.5, or 8 and 9.5, e.g., between about 7        or 7.5 and 8, e.g., between about 7.5 and 8.5, e.g., about 7.5,        e.g., about 8.5, e.g., between about 8 and 8.5, e.g., about 8.2,        e.g., a base wherein a conjugate acid of the base has a pKa        between 6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7, 8,        or 9 and 10, e.g., between about 7 and 9, e.g., between about 8        and 9, e.g., wherein the one or more bases are one or more of:        -   a) a metal citrate salt (e.g., an alkali and/or alkaline            citrate salt, e.g., an alkali citrate salt, e.g., sodium            citrate and/or potassium citrate),        -   b) a metal phosphate salt (e.g., an alkali and/or alkaline            phosphate salt, e.g., an alkali phosphate salt, e.g., sodium            phosphate (e.g., NaH₂PO₄ and/or Na₂HPO₄) and/or potassium            phosphate (e.g., KH₂PO₄ and/or K₂HPO₄), e.g., sodium            phosphate (e.g., Na₂HPO₄)),        -   c) an amine and/or a salt thereof (e.g., morpholine, an            amino acid (e.g., arginine), a mono- and/or            poly-hydroxyalkylamine, and/or a salt thereof, e.g.,            (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a            salt thereof wherein each R⁸ is independently C₁₋₈alkyl            (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g.,            —CH₃) and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene,            e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g.,            one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and each n is            independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,            tris(hydroxymethyl)aminomethane (also known as tris base)            and/or a salt thereof (e.g., tris(hydroxymethyl)aminomethane            acetate (also known as tris acetate), meglumine, and/or            diethanolamine), e.g., any of the preceding wherein a            conjugate acid of the amine and/or salt thereof has a pKa            between 6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7,            8, or 9 and 10, e.g., between about 7 and 9, e.g., between            about 8 and 9,        -   d) a metal acetate salt (e.g., an alkali and/or alkaline            acetate salt, e.g., an alkali acetate salt, e.g., sodium            acetate and/or potassium acetate),        -   e) a metal hydroxide salt (e.g., an alkali and/or alkaline            hydroxide salt, e.g., sodium hydroxide, potassium hydroxide,            calcium hydroxide, and/or magnesium hydroxide, e.g., sodium            hydroxide),        -   f) a metal carbonate and/or bicarbonate salt (e.g., an            alkali and/or alkaline carbonate salt, e.g., an alkali            and/or alkaline bicarbonate salt, e.g., sodium bicarbonate),            and/or        -   g) a metal borate salt (e.g., an alkali borate salt, e.g.,            sodium borate),    -    e.g., one or more of sodium citrate, Na₂HPO₄,        tris(hydroxymethyl)aminomethane, and a        tris(hydroxymethyl)aminomethane salt (e.g., tris acetate), e.g.,        one or more of sodium citrate, Na₂HPO₄, and        tris(hydroxymethyl)aminomethane, e.g., one or more of sodium        citrate and Na₂HPO₄, e.g., Na₂HPO₄, e.g.,        tris(hydroxymethyl)aminomethane.    -   1.5 Composition 1.3 or 1.4 wherein the composition comprises 1        or 5 mg to 200 or 500 mg of the one or more bases, e.g., from        about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150,        200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from        about 15, 20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600,        700, 800, 1000, or 1500 mg.    -   1.6 Composition 1.3-1.5 wherein the one or more bases comprise        one or more of a metal citrate salt (e.g., sodium citrate) and a        metal phosphate salt (e.g., sodium phosphate, e.g., Na₂HPO₄).    -   1.7 Composition 1.3-1.6 wherein the one or more bases comprise a        metal citrate salt (e.g., sodium citrate).    -   1.8 Composition 1.7 wherein the composition comprises 1 or 5 mg        to 200 or 500 mg of a metal citrate salt (e.g., sodium citrate),        e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75,        100, 150, 200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg,        e.g., from about 15, 20, 30, 50, or 100 to 200, 250, 400, 450,        500, 600, 700, 800, 1000, or 1500 mg.    -   1.9 Composition 1.3-1.8 wherein the one or more bases comprise a        metal phosphate salt (e.g., sodium phosphate, e.g., Na₂HPO₄).    -   1.10 Composition 1.9 wherein the composition comprises 1 or 5 mg        to 200 or 500 mg of a metal phosphate salt, e.g., sodium        phosphate, e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30,        40, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 1000,        or 1500 mg, e.g., from about 15, 20, 30, 50, or 100 to 200, 250,        400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.11 Composition 1.3-1.10 wherein the one or more bases comprise        sodium phosphate, e.g., Na₂HPO₄.    -   1.12 Composition 1.11 wherein the composition comprises 1 or 5        mg to 200 or 500 mg sodium phosphate, e.g., Na₂HPO₄, e.g., from        about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150,        200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from        about 15, 20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600,        700, 800, 1000, or 1500 mg.    -   1.13 Composition 1.3-1.12 wherein the one or more bases comprise        an amine and/or a salt thereof (e.g., morpholine, an amino acid        (e.g., arginine), a mono- and/or poly-hydroxyalkylamine, and/or        a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁-s-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        e.g., any of the preceding wherein a conjugate acid of the amine        and/or salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,        e.g., between about 6, 7, 8, or 9 and 10, e.g., between about 7        and 9, e.g., between about 8 and 9.    -   1.14 Composition 1.13 wherein the composition comprises 1 or 5        mg to 200 or 500 mg of the amine and/or a salt thereof (e.g.,        morpholine, an amino acid (e.g., arginine), a mono- and/or        poly-hydroxyalkylamine, and/or a salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., any of the        preceding wherein a conjugate acid of the amine and/or salt        thereof has a pKa between 6, 7, 8, 9, or 10 and 11, e.g.,        between about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9,        e.g., between about 8 and 9, e.g., from about 1 or 5 or 10 mg to        15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300, 350, 400,        450, 500, 1000, or 1500 mg, e.g., from about 15, 20, 30, 50, or        100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.15 Composition 1.3-1.14 wherein the one or more bases comprise        a mono- and/or poly-hydroxyalkylamine and/or a salt thereof,        e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a        salt thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine).    -   1.16 Composition 1.15 wherein the composition comprises 1 or 5        mg to 200 or 500 mg of the mono- and/or poly-hydroxyalkylamine        and/or salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75,        100, 150, 200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg,        e.g., from about 15, 20, 30, 50, or 100 to 200, 250, 400, 450,        500, 600, 700, 800, 1000, or 1500 mg.    -   1.17 Composition 1.3-1.16 wherein the one or more bases comprise        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine).    -   1.18 Composition 1.17 wherein the composition comprises 1 or 5        mg to 200 or 500 mg of (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75,        100, 150, 200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg,        e.g., from about 15, 20, 30, 50, or 100 to 200, 250, 400, 450,        500, 600, 700, 800, 1000, or 1500 mg.    -   1.19 Composition 1.3-1.18 wherein the one or more bases comprise        tris(hydroxymethyl)aminomethane and/or meglumine, e.g.,        tris(hydroxymethyl)aminomethane, e.g., meglumine.    -   1.20 Composition 1.19 wherein the composition comprises 1 or 5        mg to 200 or 500 mg tris(hydroxymethyl)aminomethane, e.g., from        about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150,        200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from        about 15, 20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600,        700, 800, 1000, or 1500 mg and/or wherein the composition        comprises 1 or 5 mg to 200 or 500 mg meglumine, e.g., from about        1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200,        250, 300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about        15, 20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700,        800, 1000, or 1500 mg.    -   1.21 Composition 1.3-1.20 wherein the one or more bases comprise        a tris(hydroxymethyl)aminomethane salt, e.g.,        tris(hydroxymethyl)aminomethane acetate.    -   1.22 Composition 1.21 wherein the composition comprises 1 or 5        mg to 200 or 500 mg of the tris(hydroxymethyl)aminomethane salt        (e.g., tris(hydroxymethyl)aminomethane acetate), e.g., from        about 1 or 5 or 10 mg to 15, 20, 25, 30, 50, 75, 100, 150, 200,        250, 300, 350, 400, 450, 500, 1000, or 1500 mg, e.g, from about        15, 20, 30, or 50 to 100, 200, 250, 400, 450, 500, 600, or 700        mg, e.g., from about 1 or 5 mg to 200 or 500 mg        tris(hydroxymethyl)aminomethane acetate, e.g., from about 1 or 5        or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300,        350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15, 20,        30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000,        or 1500 mg.    -   1.23 Composition 1.3-1.22 wherein the one or more bases comprise        a base, e.g., an amine and/or a salt thereof, wherein a        conjugate acid of the base has a pKa between 6, 7, 8, 9, or 10        and 11, e.g., between about 6, 7, 8, or 9 and 10, e.g., between        about 7 and 9, e.g., between about 8 and 9.    -   1.24 Composition 1.23 wherein the composition comprises 1 or 5        mg to 200 or 500 mg of a base, e.g., an amine and/or a salt        thereof, wherein a conjugate acid of the base has a pKa between        6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7, 8, or 9 and        10, e.g., between about 7 and 9, e.g., between about 8 and 9,        e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75,        100, 150, 200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg,        e.g., from about 15, 20, 30, 50, or 100 to 200, 250, 400, 450,        500, 600, 700, 800, 1000, or 1500 mg.    -   1.25 Composition 1.1-1.24 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the one or more bases is at least 1:1,        e.g, wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the one or more bases is at least 2:1.    -   1.26 Composition 1.1-1.25 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the one or more bases is at least 1:2,        e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8,        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.27 Composition 1.26 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to a metal citrate salt (e.g., sodium        citrate) is at least 1:2, e.g., at least about 1:2, 1:3, 1:4, or        1:5 to 1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at        least about 1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20,        or 1:30, e.g., at least about 1:2.5, e.g., at least about 1:5,        e.g. at least about 1:10.    -   1.28 Composition 1.26 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to a metal phosphate salt (e.g., sodium        phosphate, e.g., Na₂HPO₄) is at least 1:1, e.g., at least 1:2,        e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.29 Composition 1.26 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the amine and/or salt thereof (e.g.,        morpholine, an amino acid (e.g., arginine), a mono- and/or        poly-hydroxyalkylamine, and/or salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., any of the        preceding wherein a conjugate acid of the amine and/or salt        thereof has a pKa between 6, 7, 8, 9, or 10 and 11, e.g.,        between about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9,        e.g., between about 8 and 9, is at least 1:2, e.g., at least        about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to 1:10, 1:15,        1:20, or 1:30, e.g., at least about 1:2.5 to 1:5, 1:6, 1:7, 1:8,        1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5,        e.g., at least about 1:5, e.g. at least about 1:10.    -   1.30 Composition 1.29 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the mono- and/or poly-hydroxyalkylamine        and/or salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C-s-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        is at least 1:2, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to        1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.31 Composition 1.30 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        is 1:2, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7,        1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to        1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at        least about 1:2.5, e.g., at least about 1:5, e.g. at least about        1:10.    -   1.32 Composition 1.31 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to tris(hydroxymethyl)aminomethane is at        least 1:2, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6,        1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.33 Composition 1.31 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the tris(hydroxymethyl)aminomethane salt        (e.g, tris(hydroxymethyl)aminomethane acetate) is at least 1:2,        e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10,        e.g., wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to tris(hydroxymethyl)aminomethane acetate        is at least 1:2, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to        1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.34 Composition 1.26 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to a base, e.g., an amine and/or a salt        thereof, wherein a conjugate acid of the base has a pKa between        6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7, 8, or 9 and        10, e.g., between about 7 and 9, e.g., between about 8 and 9, is        at least 1:2, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6,        1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.35 Composition I or 1.1-1.34 wherein the composition comprises        one or more bulking agents which may provide an adequate        structure to the lyophilized cake, e.g., one or more of        mannitol, lactose, sucrose, trehalose, sorbitol, glucose,        raffinose, arginine, glycine, histidine, dextran (e.g., dextran        40), polyvinylpyrrolidone, polyethylene glycol, and        polypropylene glycol, e.g., one or more of mannitol, glucose,        sucrose, lactose, trehalose, and dextran (e.g., dextran 40).    -   1.36 Composition I or 1.1-1.35 wherein the composition comprises        5 or 10 or 50 mg to 2 or 5 g of one or more bulking agents,        e.g., from about 50 or 100 mg to 200, 300, 500, or 800 mg, or 1,        1.5, 2, 3, 4, or 5 g of one or more bulking agents.    -   1.37 Composition I or 1.1-1.36 wherein the composition comprises        dextran (e.g., dextran 40).    -   1.38 Composition 1.37 wherein the composition comprises 5 or 10        or 50 mg to 2 or 5 g dextran (e.g., dextran 40), e.g., from        about 50 mg or 100 mg to 200, 300, 500, or 800 mg, or 1, 1.5, 2,        3, 4, or 5 g dextran (e.g., dextran 40).    -   1.39 Composition I or 1.1-1.38 wherein the composition comprises        one or more solubilizing agents, e.g., ethylenediamine        tetraacetic acid (EDTA) or a salt thereof (e.g., calcium        disodium EDTA, disodium EDTA, sodium EDTA), alpha cyclodextrin,        hydroxypropyl-β-cyclodextrin, polysorbate 80, tert-butanol,        isopropanol, dichloromethane, ethanol, acetone, and glycerol;        one or more collapse temperature modifiers which may shift the        overall collapse temperature higher, e.g., one or more of        dextran, Ficoll®, gelatin, and hydroxyethyl starch; one or more        tonicity modifiers, e.g., one or more of sodium chloride,        potassium chloride, sucrose, mannitol, glucose, and lactose; and        one or more antimicrobial agents, e.g., one or more of benzyl        alcohol, phenol, 2-phenoxyethanol, m-cresol, chlorobutanol,        parabens (e.g., methyl paraben, ethyl paraben, propyl paraben),        benzalkonium chloride, benzethonium chloride, myristyl        gamma-picolinium salt (e.g., myristyl gamma-picolinium        chloride), and organomercury compounds and salts (e.g., phenyl        mercuric acetate, phenyl mercuric borate, phenyl mercuric        nitrate, and thimerosal).    -   1.40 Composition I or 1.1-1.39 wherein the composition is a        solid, e.g., the pharmaceutically acceptable excipient, e.g, the        one or more bases is a solid.    -   1.41 Composition I or 1.1-1.40 wherein the composition is        lyophilized.    -   1.42 Composition I or 1.1-1.41 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is lyophilized, e.g., by freezing, primary        drying, and secondary drying.    -   1.43 Composition 1.42 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is lyophilized, e.g., by freezing, primary        drying, and secondary drying, prior to admixture with the        pharmaceutically acceptable excipient.    -   1.44 Composition I or 1.1-1.43 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is crystalline.    -   1.45 Composition I or 1.1-1.44 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is amorphous.    -   1.46 Composition I or 1.1-1.45 which is suitable for        constitution, or reconstitution if lyophilized, with a solvent,        e.g., an aqueous solution, into a pharmaceutically acceptable        liquid (e.g., a solution or suspension, e.g., a solution).    -   1.47 Composition I or 1.1-1.46 wherein the composition is        admixed with a solvent, e.g., a sterile solution, e.g., sterile        water for injection, a sterile solution comprising dextrose        (e.g., dextrose injection 5%), a sterile solution comprising        sodium chloride (e.g., 0.9% sodium chloride injection), a        sterile solution comprising benzyl alcohol (e.g., bacteriostatic        water for injection with benzyl alcohol or bacteriostatic sodium        chloride for injection with benzyl alcohol), or Lactated        Ringer's.    -   1.48 Composition I or 1.1-1.47 wherein the composition is        admixed with 0.5 to 500 mL solvent, e.g., an aqueous solution,        e.g., from about 1 or 2 mL to 500 mL, e.g., from about 1 or 2 mL        to 5, 10, 25, 30, 35, 50, 75, 100, 150, 200, 300 or 500 mL,        e.g., from about 1 or 2 mL to 5, 10, 25, 50, 75, 100, or 200 mL,        e.g., from about 3.5 or 5 to 10, 25, 50, or 100 mL, e.g., about        3.5 or 35 mL.    -   1.49 Composition I or 1.1-1.48 wherein the composition is        admixed with 0.5 to 500 mL sterile solution, e.g., sterile water        for injection, a sterile solution comprising dextrose (e.g.,        dextrose injection 5%), a sterile solution comprising sodium        chloride (e.g., 0.9% sodium chloride injection), a sterile        solution comprising benzyl alcohol (e.g., bacteriostatic water        for injection with benzyl alcohol or bacteriostatic sodium        chloride for injection with benzyl alcohol), or Lactated        Ringer's, e.g., from about 1 or 2 mL to 500 mL, e.g., from about        1 or 2 mL to 5, 10, 25, 30, 35, 50, 75, 100, 150, 200, 300 or        500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 50, 75, 100, or        200 mL, e.g., from about 3.5 or 5 to 10, 25, 50, or 100 mL,        e.g., about 3.5 or 35 mL.    -   1.50 Composition I or 1.1-1.49 wherein the composition is        admixed with sterile water for injection or a sterile solution        comprising sodium chloride (e.g., 0.9% sodium chloride        injection).    -   1.51 Composition I or 1.1-1.50 wherein the composition is        admixed with sterile water for injection.    -   1.52 Composition 1.51 wherein the composition is admixed with        0.5 to 500 mL sterile water for injection, e.g., from about 1 or        2 mL to 500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 30, 35,        50, 75, 100, 150, 200, 300 or 500 mL, e.g., from about 1 or 2 mL        to 5, 10, 25, 50, 75, 100, or 200 mL, e.g., from about 3.5 or 5        to 10, 25, 50, or 100 mL, e.g., about 3.5 or 35 mL.    -   1.53 Composition I or 1.1-1.52 wherein the composition is        admixed with a sterile solution comprising sodium chloride        (e.g., 0.9% sodium chloride injection).    -   1.54 Composition 1.53 wherein the composition is admixed with        0.5 to 500 mL a sterile solution comprising sodium chloride        (e.g., 0.9% sodium chloride injection), e.g., from about 1 or 2        mL to 500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 30, 35,        50, 75, 100, 150, 200, 300 or 500 mL, e.g., from about 1 or 2 mL        to 5, 10, 25, 50, 75, 100, or 200 mL, e.g., from about 3.5 or 5        to 10, 25, 50, or 100 mL, e.g., about 3.5 or 35 mL.    -   1.55 Composition 1.47-1.54 wherein the composition comprises        Formula II

-   -   1.56 Composition 1.47-1.55 wherein the composition comprises at        least a 1:1 molar ratio of Formula II to a cation of the base,        e.g., at least a 2:1 molar ratio of Formula II to the cation of        the base.    -   1.57 Composition 1.47-1.54 wherein the composition comprises        Formula III

-   -   1.58 Composition 1.47-1.54 or 1.57 wherein the composition        comprises at least a 1:2 molar ratio of Formula III to a cation        of the base, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6,        1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.59 Composition 1.47-1.58 wherein the concentration of Formula        II or Formula III, e.g., the concentration of Formula II, e.g,        the concentration of Formula III, is 0.01 or 0.02 or 0.05 or 0.1        or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5        to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175,        200, 250 mM, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20,        25, 40, 50 or 60 mM, e.g., from about 5, 10, 15, 20, 25, or 50        to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20,        or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM.    -   1.60 Composition 1.47-1.59 wherein the solvent, e.g., the        sterile solution, comprises one or more pharmaceutically        acceptable bases, e.g., a base wherein upon dissolution of the        composition in the solvent, e.g, aqueous solution, the        composition has a pH between 7, 7.5, or 8 and 10.5, e.g.,        between about 7, 7.5, or 8 and 9.5, e.g., between about 7 or 7.5        and 8, e.g., between about 7.5 and 8.5, e.g., about 7.5, e.g.,        about 8.5, e.g., between about 8 and 8.5, e.g., about 8.2, e.g.,        a base wherein a conjugate acid of the pharmaceutically        acceptable base has a pKa between 6, 7, 8, 9, or 10 and 11,        e.g., between about 6, 7, 8, or 9 and 10, e.g., between about 7        and 9, e.g., between about 8 and 9, e.g., wherein the one or        more pharmaceutically acceptable bases are one or more of:        -   a) a C₁₋₈-alkyl mono-, di-, or tri-carboxylic acid salt,            e.g., a citrate salt, e.g, a metal citrate salt (e.g., an            alkali and/or alkaline citrate salt, e.g., an alkali citrate            salt, e.g., sodium citrate and/or potassium citrate), e.g.,            a tartrate salt (e.g., a metal tartrate salt, an alkali            tartrate, e.g., sodium tartrate), e.g., a succinate salt            (e.g., a metal succinate salt, e.g., an alkali succinate,            e.g., disodium succinate), and/or e.g., a lactate salt            (e.g., a metal lactate salt, e.g., an alkali lactate, e.g.,            sodium lactate),        -   b) a phosphate salt, e.g., a metal phosphate salt (e.g., an            alkali and/or alkaline phosphate salt, e.g., an alkali            phosphate salt, e.g., sodium phosphate (e.g., NaH₂PO₄ and/or            Na₂HPO₄) and/or potassium phosphate (e.g., KH₂PO₄ and/or            K₂HPO₄)),        -   c) an amine and/or a salt thereof (e.g., morpholine,            piperazine, benethamine, benzathine, trimethylglycine,            hydrabamine, 4-(2-hydroxyethyl)morpholine,            1-2-hydroxyethyl)-pyrrolidine, an amino acid (e.g., arginine            and/or lysine), a mono- and/or poly-hydroxyalkylamine,            and/or a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,            [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each R⁸ is            independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,            e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene            (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—,            e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is            —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,            5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known            as tris base) and/or a salt thereof (e.g.,            tris(hydroxymethyl)aminomethane acetate (also known as tris            acetate), meglumine, dimethylethanolamine, diethylamine,            diethylethanolamine, and/or diethanolamine), e.g., any of            the preceding wherein a conjugate acid of the amine and/or            salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,            e.g., between about 6, 7, 8, or 9 and 10, e.g., between            about 7 and 9, e.g., between about 8 and 9,        -   d) a metal chloride salt (e.g., zinc chloride),        -   e) an acetate salt, e.g., a metal acetate salt (e.g., an            alkali and/or alkaline acetate salt, e.g., an alkali acetate            salt, e.g., sodium acetate and/or potassium acetate),        -   f) a hydroxide and/or alkoxide salt, e.g., a metal hydroxide            and/or alkoxide salt (.g., a quarternary ammonium hydroxide,            e.g., ammonium hydroxide and/or choline hydroxide, lithium            hydroxide, aluminum hydroxide, e.g., an alkali and/or            alkaline hydroxide salt, e.g., sodium hydroxide, potassium            hydroxide, calcium hydroxide, magnesium hydroxide, and/or            magnesium ethoxide e.g., sodium hydroxide),        -   g) a carbonate and/or bicarbonate salt, e.g., a metal            carbonate and/or metal bicarbonate salt (e.g., an alkali            and/or alkaline carbonate salt, e.g., an alkali and/or            alkaline bicarbonate salt, e.g., sodium bicarbonate), and/or        -   h) a metal borate salt (e.g., an alkali borate salt, e.g.,            sodium borate),    -    e.g., one or more of sodium citrate, Na₂HPO₄,        tris(hydroxymethyl)aminomethane, and a        tris(hydroxymethyl)aminomethane salt (e.g., tris acetate), e.g.,        one or more of sodium citrate, Na₂HPO₄, and        tris(hydroxymethyl)aminomethane, e.g., one or more of sodium        citrate and Na₂HPO₄, e.g., Na₂HPO₄, e.g.,        tris(hydroxymethyl)aminomethane.    -   1.61 Composition 1.47-1.60 wherein the solvent, e.g., the        sterile solution, comprises one or more pharmaceutically        acceptable bases, e.g., a base wherein upon dissolution of the        composition in the solvent, e.g., the sterile solution, the        composition has a pH between 7, 7.5, or 8 and 10.5, e.g.,        between about 7, 7.5, or 8 and 9.5, e.g., between about 7 or 7.5        and 8, e.g., between about 7.5 and 8.5, e.g., about 7.5, e.g.,        about 8.5, e.g., between about 8 and 8.5, e.g., about 8.2, e.g.,        a base wherein a conjugate acid of the pharmaceutically        acceptable base has a pKa between 6, 7, 8, 9, or 10 and 11,        e.g., between about 6, 7, 8, or 9 and 10, e.g., between about 7        and 9, e.g., between about 8 and 9, e.g., wherein the one or        more pharmaceutically acceptable bases is one or more of:        -   a) a metal citrate salt (e.g., an alkali and/or alkaline            citrate salt, e.g., an alkali citrate salt, e.g., sodium            citrate and/or potassium citrate),        -   b) a metal phosphate salt (e.g., an alkali and/or alkaline            phosphate salt, e.g., an alkali phosphate salt, e.g., sodium            phosphate (e.g., NaH₂PO₄ and/or Na₂HPO₄) and/or potassium            phosphate (e.g., KH₂PO₄ and/or K₂HPO₄)),        -   c) an amine and/or a salt thereof (e.g., morpholine, an            amino acid (e.g., arginine), a mono- and/or            poly-hydroxyalkylamine, and/or a salt thereof, e.g.,            (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a            salt thereof wherein each R⁸ is independently C₁₋₈alkyl            (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g.,            —CH₃) and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene,            e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g.,            one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and each n is            independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,            tris(hydroxymethyl)aminomethane (also known as tris base)            and/or a salt thereof (e.g., tris(hydroxymethyl)aminomethane            acetate (also known as tris acetate), meglumine, and/or            diethanolamine), e.g., any of the preceding wherein a            conjugate acid of the amine and/or salt thereof has a pKa            between 6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7,            8, or 9 and 10, e.g., between about 7 and 9, e.g., between            about 8 and 9,        -   d) a metal acetate salt (e.g., an alkali and/or alkaline            acetate salt, e.g., an alkali acetate salt, e.g., sodium            acetate and/or potassium acetate),        -   e) a metal hydroxide salt (e.g., an alkali and/or alkaline            hydroxide salt, e.g., sodium hydroxide, potassium hydroxide,            calcium hydroxide, and/or magnesium hydroxide, e.g., sodium            hydroxide),        -   f) a metal carbonate and/or bicarbonate salt (e.g., an            alkali and/or alkaline carbonate salt, e.g., an alkali            and/or alkaline bicarbonate salt, e.g., sodium bicarbonate),            and/or        -   g) a metal borate salt (e.g., an alkali borate salt, e.g.,            sodium borate),    -    e.g., one or more of sodium citrate, Na₂HPO₄,        tris(hydroxymethyl)aminomethane, and a        tris(hydroxymethyl)aminomethane salt (e.g., tris acetate), e.g.,        one or more of sodium citrate, Na₂HPO₄, and        tris(hydroxymethyl)aminomethane, e.g., one or more of sodium        citrate and Na₂HPO₄, e.g., Na₂HPO₄, e.g.,        tris(hydroxymethyl)aminomethane.    -   1.62 Composition 1.61 wherein the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and the base, e.g., sodium citrate, sodium        phosphate (e.g., Na₂HPO₄), tris(hydroxymethyl)aminomethane,        tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate), and/or meglumine form        a salt.    -   1.63 Composition 1.60-1.62 wherein the solvent, e.g., the        sterile solution, comprises 1 or 5 mg to 200 or 500 mg of the        one or more bases, e.g., from about 1 or 5 or 10 mg to 15, 20,        25, 30, 40, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500,        1000, or 1500 mg, e.g., from about 15, 20, 30, 50, or 100 to        200, 250, 400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.64 Composition 1.60-1.63 wherein the concentration of each of        the one or more bases is 0.01 or 0.02 or 0.05 or 0.1 or 0.5 or 1        or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to 1, 2, 5,        10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175, 200, 250 mM,        or 1000 mM e.g. from about 1 to 2, 5, 10, 15, 20, 25, 40, 50 or        60 mM, e.g., from about 5, 10, 15, 20, 25, or 50 to 100, 200,        250, 300, 400, 500, or 1000 mM, e.g., about 2, 20, or 200 mM,        e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g., wherein the        concentration of each of the one or more bases is 2 or 3 to 5,        6, 8, 10, 15 or 20 equivalents of Formula II, e.g., about 2.5 or        5 to 10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of each of the one or more bases is 2 or 3 to 5,        6, 8, 10, 15 or 20 equivalents of Formula III, e.g., about 5 to        10, e.g. about 5, e.g., about 10.    -   1.65 Composition 1.60-1.64 wherein the one or more bases        comprise one or more of a metal citrate salt (e.g., sodium        citrate) and a metal phosphate salt (e.g., sodium phosphate,        e.g., Na₂HPO₄).    -   1.66 Composition 1.60-1.65 wherein the one or more bases        comprise a metal citrate salt (e.g., sodium citrate).    -   1.67 Composition 1.66 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of the metal        citrate salt (e.g., sodium citrate), e.g., from about 1 or 5 or        10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300,        350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15, 20,        30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000,        or 1500 mg.    -   1.68 Composition 1.66 wherein the concentration of the metal        citrate salt (e.g., sodium citrate) is 0.01 or 0.02 or 0.05 or        0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or        0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150,        175, 200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15,        20, 25, 40, 50 or 60 mM, e. e.g., from about 5, 10, 15, 20, 25,        or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about        2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM,        e.g., wherein the concentration of the metal citrate salt is 2        or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula II, e.g.,        about 2.5 or 5 to 10, e.g. about 2.5, e.g., about 5, e.g.,        wherein the concentration of the metal citrate salt is 2 or 3 to        5, 6, 8, 10, 15 or 20 equivalents of Formula III, e.g., about 5        to 10, e.g. about 5, e.g., about 10.    -   1.69 Composition 1.60-1.68 wherein the one or more bases        comprise a metal phosphate salt (e.g., sodium phosphate, e.g.,        Na₂HPO₄).    -   1.70 Composition 1.69 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of the metal        phosphate salt (e.g., sodium phosphate, e.g., Na₂HPO₄), e.g.,        from about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100,        150, 200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg, e.g.,        from about 15, 20, 30, 50, or 100 to 200, 250, 400, 450, 500,        600, 700, 800, 1000, or 1500 mg.    -   1.71 Composition 1.69 wherein the concentration of the metal        phosphate salt (e.g., sodium phosphate, e.g., Na₂HPO₄), is 0.01        or 0.02 or 0.05 or 0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from        about 0.01 or 0.1 or 0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60,        75, 100, 125, 150, 175, 200, 250, or 1000 mM, e.g. from about 1        to 2, 5, 10, 15, 20, 25, 40, 50 or 60 mM, e.g., from about 5,        10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500, or 1000        mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50, 500,        500, or 1000 mM, e.g., wherein the concentration of each of the        metal phosphate salt (e.g., sodium phosphate, e.g., Na₂HPO₄) is        2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula II, e.g.,        about 2.5 or 5 to 10, e.g. about 2.5, e.g., about 5, e.g.,        wherein the concentration of the metal phosphate salt (e.g.,        sodium phosphate, e.g., Na₂HPO₄) is 2 or 3 to 5, 6, 8, 10, 15 or        20 equivalents of Formula III, e.g., about 5 to 10, e.g. about        5, e.g., about 10.    -   1.72 Composition 1.60-1.71 wherein the one or more bases        comprise an amine and/or a salt thereof (e.g., morpholine, an        amino acid (e.g., arginine), a mono- and/or        poly-hydroxyalkylamine, and/or a salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., any of the        preceding wherein a conjugate acid of the amine and/or salt        thereof has a pKa between 6, 7, 8, 9, or 10 and 11, e.g.,        between about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9,        e.g., between about 8 and 9.    -   1.73 Composition 1.72 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of the amine        and/or a salt thereof (e.g., morpholine, an amino acid (e.g.,        arginine), a mono- and/or poly-hydroxyalkylamine, and/or a salt        thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N,        and/or a salt thereof wherein each R⁸ is independently C₁₋₈alkyl        (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃)        and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g.,        C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is        —CH₃ and another R⁸ is —(CH₂)₆—) and each n is independently 1-8        (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        e.g., any of the preceding wherein a conjugate acid of the amine        and/or salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,        e.g., between about 6, 7, 8, or 9 and 10, e.g., between about 7        and 9, e.g., between about 8 and 9, e.g., from about 1 or 5 or        10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300,        350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15, 20,        30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000,        or 1500 mg.    -   1.74 Composition 1.72 wherein the concentration of the amine        and/or a salt thereof (e.g., morpholine, an amino acid (e.g.,        arginine), a mono- and/or poly-hydroxyalkylamine, and/or a salt        thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]3N,        and/or a salt thereof wherein each R⁸ is independently C₁₋₈alkyl        (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃)        and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g.,        C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is        —CH₃ and another R⁸ is —(CH₂)₆—) and each n is independently 1-8        (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        e.g., any of the preceding wherein a conjugate acid of the amine        and/or salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,        e.g., between about 6, 7, 8, or 9 and 10, e.g., between about 7        and 9, e.g., between about 8 and 9, is 0.01 or 0.02 or 0.05 or        0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or        0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150,        175, 200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15,        20, 25, 40, 50 or 60 mM, e.g., from about 5, 10, 15, 20, 25, or        50 to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2,        20, or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM,        e.g., wherein the concentration of each of the amine and/or a        salt thereof (e.g., morpholine, an amino acid (e.g., arginine),        a mono- and/or poly-hydroxyalkylamine, and/or a salt thereof,        e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a        salt thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., any of the        preceding wherein a conjugate acid of the amine and/or salt        thereof has a pKa between 6, 7, 8, 9, or 10 and 11, e.g.,        between about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9,        e.g., between about 8 and 9 is 2 or 3 to 5, 6, 8, 10, 15 or 20        equivalents of Formula II, e.g., about 2.5 or 5 to 10, e.g.        about 2.5, e.g., about 5, e.g., wherein the concentration of        each of the amine and/or a salt thereof (e.g., morpholine, an        amino acid (e.g., arginine), a mono- and/or        poly-hydroxyalkylamine, and/or a salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., any of the        preceding wherein a conjugate acid of the amine and/or salt        thereof has a pKa between 6, 7, 8, 9, or 10 and 11, e.g.,        between about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9,        e.g., between about 8 and 9 is 2 or 3 to 5, 6, 8, 10, 15 or 20        equivalents of Formula III, e.g., about 5 to 10, e.g. about 5,        e.g., about 10.    -   1.75 Composition 1.60-1.74 wherein the one or more bases        comprise a mono- and/or poly-hydroxyalkylamine and/or a salt        thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N,        and/or a salt thereof wherein each R⁸ is independently C₁₋₈alkyl        (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃)        and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g.,        C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is        —CH₃ and another R⁸ is —(CH₂)₆—) and each n is independently 1-8        (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine).    -   1.76 Composition 1.75 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of the mono-        and/or poly-hydroxyalkylamine and/or salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., from about 1        or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250,        300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15,        20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800,        1000, or 1500 mg.    -   1.77 Composition 1.75 wherein the concentration of the mono-        and/or poly-hydroxyalkylamine and/or salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), is 0.01 or 0.02 or        0.05 or 0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or        0.1 or 0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125,        150, 175, 200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10,        15, 20, 25, 40, 50 or 60 mM, e.g., from about 5, 10, 15, 20, 25,        or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about        2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM,        e.g., wherein the concentration of the mono- and/or        poly-hydroxyalkylamine and/or salt thereof, e.g., (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]3N, and/or salt thereof wherein        each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine) is 2 or 3 to 5, 6,        8, 10, 15 or 20 equivalents of Formula II, e.g., about 2.5 or 5        to 10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of the mono- and/or poly-hydroxyalkylamine and/or        salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine)        is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula III,        e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.78 Composition 1.60-1.77 wherein the one or more bases        comprise (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or        a salt thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine).    -   1.79 Composition 1.78 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein        each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., from about 1        or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250,        300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15,        20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800,        1000, or 1500 mg.    -   1.80 Composition 1.78 wherein the concentration of        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]3N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), is 0.01 or 0.02 or        0.05 or 0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or        0.1 or 0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125,        150, 175, 200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10,        15, 20, 25, 40, 50 or 60 mM, e.g., from about 5, 10, 15, 20, 25,        or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about        2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM,        e.g., wherein the concentration of (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein        each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethan acetate (also known as tris        acetate), meglumine, and/or diethanolamine) is 2 or 3 to 5, 6,        8, 10, 15 or 20 equivalents of Formula II, e.g., about 2.5 or 5        to 10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N,        and/or a salt thereof wherein each R⁸ is independently C₁₋₈alkyl        (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃)        and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g.,        C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is        —CH₃ and another R⁸ is —(CH₂)₆—) and each n is independently 1-8        (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine)        is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula III,        e.g., about 5 to 10, e.g. about 5, e.g., about 10    -   1.81 Composition 1.60-1.80 wherein the one or more bases        comprise tris(hydroxymethyl)aminomethane and/or meglumine, e.g.,        tris(hydroxymethyl)aminomethane, e.g., meglumine.    -   1.82 Composition 1.81 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of        tris(hydroxymethyl)aminomethane, e.g., from about 1 or 5 or 10        mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300, 350,        400, 450, 500, 1000, or 1500 mg, e.g, from about 15, 20, 30, or        50 to 100, 200, 250, 400, 450, 500, 600, or 700 mg and/or        wherein the composition comprises 1 or 5 mg to 200 or 500 mg        meglumine, e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30,        40, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 1000,        or 1500 mg, e.g., from about 15, 20, 30, 50, or 100 to 200, 250,        400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.83 Composition 1.81 wherein the concentration of        tris(hydroxymethyl)aminomethane is 0.01 or 0.02 or 0.05 or 0.1        or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5        to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175,        200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25,        40, 50 or 60 mM, e.g., from about 5, 10, 15, 20, 25, or 50 to        100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20, or        200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of tris(hydroxymethyl)aminomethane is        2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula II, e.g.,        about 2.5 or 5 to 10, e.g. about 2.5, e.g., about 5, e.g.,        wherein the concentration of tris(hydroxymethyl)aminomethane is        2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula III,        e.g., about 5 to 10, e.g. about 5, e.g., about 10 and/or wherein        the concentration of tris(hydroxymethyl)aminomethane is 0.01 or        0.02 or 0.05 or 0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about        0.01 or 0.1 or 0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75,        100, 125, 150, 175, 200, 250, or 1000 mM, e.g. from about 1 to        2, 5, 10, 15, 20, 25, 40, 50 or 60 mM, e.g., from about 5, 10,        15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM,        e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500,        or 1000 mM, e.g., wherein the concentration of meglumine is 2 or        3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula II, e.g.,        about 2.5 or 5 to 10, e.g. about 2.5, e.g., about 5, e.g.,        wherein the concentration of meglumine is 2 or 3 to 5, 6, 8, 10,        15 or 20 equivalents of Formula III, e.g., about 5 to 10, e.g.        about 5, e.g., about 10.    -   1.84 Composition 1.60-1.83 wherein the one or more bases        comprise a tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate).    -   1.85 Composition 1.84 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of a        tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate), e.g., from about 1 or        5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250,        300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15,        20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800,        1000, or 1500 mg.    -   1.86 Composition 1.84 wherein the concentration of the        tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate) is 0.01 or 0.02 or 0.05        or 0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1        or 0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125,        150, 175, 200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10,        15, 20, 25, 40, 50 or 60 mM, e.g., from about 5, 10, 15, 20, 25,        or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about        2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM,        e.g., wherein the concentration of the        tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate) is 2 or 3 to 5, 6, 8,        10, 15 or 20 equivalents of Formula II, e.g., about 2.5 or 5 to        10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of the tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate) is 2 or 3 to 5, 6, 8,        10, 15 or 20 equivalents of Formula III, e.g., about 5 to 10,        e.g. about 5, e.g., about 10.    -   1.87 Composition 1.60-1.86 wherein the one or more bases        comprise a buffering agent, e.g., an amine and/or a salt        thereof, wherein a conjugate acid of the base has a pKa between        6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7, 8, or 9 and        10, e.g., between about 7 and 9, e.g., between about 8 and 9.    -   1.88 Composition 1.87 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of the base,        e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75,        100, 150, 200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg,        e.g., from about 15, 20, 30, 50, or 100 to 200, 250, 400, 450,        500, 600, 700, 800, 1000, or 1500 mg.    -   1.89 Composition 1.87 wherein the concentration of the base is        0.01 or 0.02 or 0.05 or 0.1 or 0.5 or 1 or 2 to 250 mM, e.g.,        from about 0.01 or 0.1 or 0.5 to 1, 2, 5, 10, 15, 20, 25, 40,        50, 60, 75, 100, 125, 150, 175, 200, 250, or 1000 mM, e.g. from        about 1 to 2, 5, 10, 15, 20, 25, 40, 50 or 60 mM, e.g., from        about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500,        or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., wherein the concentration of the one        or more bases is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of        Formula II, e.g., about 2.5 or 5 to 10, e.g. about 2.5, e.g.,        about 5, e.g., wherein the concentration of the one or more        bases is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula        III, e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.90 Composition 1.44-1.89 wherein the solvent, e.g., the        sterile solution comprises one or more bulking agents, e.g., one        or more of maltose, mannose, ribose, cyclodextrin, mannitol,        lactose, sucrose, trehalose, sorbitol, glucose, raffinose,        arginine, glycine, histidine, dextran (e.g., dextran 40),        polyvinylpyrrolidone, polyethylene glycol, and polypropylene        glycol, e.g., one or more of mannitol, glucose, sucrose,        lactose, trehalose, and dextran (e.g., dextran 40).    -   1.91 Composition 1.44-1.90 wherein the solvent, e.g., the        sterile solution, comprises 5 or 10 or 50 mg to 2 or 5 g of one        or more bulking agents, e.g., from about 50 or 100 mg to 200,        300, 500, or 800 mg, or 1, 1.5, 2, 3, 4, or 5 g of one or more        bulking agents.    -   1.92 Composition 1.44-1.91 wherein the solvent, e.g., the        sterile solution, comprises dextran (e.g., dextran 40).    -   1.93 Composition 1.92 wherein the solvent, e.g. the sterile        solution, comprises 5 or 10 or 50 mg to 2 or 5 g dextran (e.g.,        dextran 40), e.g., from about 50 or 100 mg to 200, 300, 500, or        800 mg, or 1, 1.5, 2, 3, 4, or 5 g dextran (e.g., dextran 40).    -   1.94 Composition 1.44-1.93 wherein the solvent, e.g., the        sterile solution, comprises one or more solubilizing agents,        e.g., ethylenediamine tetraacetic acid (EDTA) or a salt thereof        (e.g., calcium disodium EDTA, disodium EDTA, sodium EDTA), alpha        cyclodextrin, hydroxypropyl-β-cyclodextrin, polysorbate 80,        tert-butanol, isopropanol, dichloromethane, ethanol, acetone,        and glycerol; one or more collapse temperature modifiers which        may shift the overall collapse temperature higher, e.g., one or        more of dextran, Ficoll®, gelatin, and hydroxyethyl starch; one        or more tonicity modifiers, e.g., one or more of sodium        chloride, potassium chloride, sucrose, mannitol, and glucose;        and one or more antimicrobial agents, e.g., one or more of        benzyl alcohol, phenol, 2-phenoxyethanol, m-cresol,        chlorobutanol, parabens (e.g., methyl paraben, ethyl paraben,        propyl paraben), benzalkonium chloride, benzethonium chloride,        myristyl gamma-picolinium salt (e.g., myristyl gamma-picolinium        chloride), and organomercury compounds and salts (e.g., phenyl        mercuric acetate, phenyl mercuric borate, phenyl mercuric        nitrate, and thimerosal).    -   1.95 Composition 1.44-1.94 wherein the pH after admixture with        the solvent, e.g., the aqueous solution, is between pH 7 and pH        10.5, e.g., between pH 7 and pH 9.5, e.g., between pH 7 and pH        8, e.g., between 7.5 and 8.5, e.g., 7.5, e.g., 8.5, e.g., 8.2.    -   1.96 Composition 1.44-1.95 wherein the pH after admixture with        the solvent, e.g., the aqueous solution, is further adjusted,        e.g., adjusted to achieve a pH between pH 7 and pH 10.5, e.g.,        between pH 7 and pH 9.5, e.g., between pH 7 and pH 8, e.g.,        between 7.5 and 8.5, e.g., 7.5, e.g., 8.5, e.g., 8.2, e.g.,        wherein the pH is adjusted with NaOH.    -   1.97 Composition 1.44-1.96 wherein the composition is filtered        after admixture with the solvent, e.g., the aqueous solution, to        remove particles and microbes, e.g., filtered prior to        injection.    -   1.98 Composition 1.44-1.97 wherein the composition is        administered about 24 hours, 12 hours, 10 hours, 8 hours, 2        hours, 1 hour, 30 minutes, 20 minutes, 15 minutes, 10 minutes, 5        minutes, 3 minutes, 2 minutes or 1 minute or less after        admixture.    -   1.99 Composition 1.44-1.98 wherein the composition comprises        Formula II

-   -   1.100 Composition 1.44-1.99 wherein the composition comprises at        least a 1:1 molar ratio of Formula II to a cation of the base.    -   1.101 Composition 1.44-1.98 wherein the composition comprises        Formula III

-   -   1.102 Composition 1.44-1.98 or 1.101 wherein the composition        comprises at least a 1:2 molar ratio of Formula III to a cation        of the base, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6,        1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.103 Composition I or 1.1-1.102 wherein the composition is for        injection, e.g., subcutaneously, intramuscularly, intravenously,        or intrathecally, e.g., intramuscularly or intravenously, e.g.,        a bolus injected subcutaneously, intramuscularly, intravenously,        or intrathecally.    -   1.104 Composition 1.103 wherein the composition is for injection        intravenously, e.g., IV bolus and/or IV infusion, e.g., IV bolus        followed by IV infusion, e.g., a loading bolus (e.g., 10 or 20        to 30, 50, 70, 75, 100, 140, 150, 200, 300 or 400 mg per day        administered by a loading bolus dose, e.g., about 50 to 200 or        250 mg per day administered by a loading bolus dose, e.g., about        70 to 140 mg per day administered by a loading bolus dose, e.g.,        a concentration of the dissolved salt administered by a loading        bolus dose of 1 to 4, 5, 8, 10, 15, 20, 30, or 50 mM per day,        e.g., a concentration of the dissolved salt administered by a        loading bolus dose of about 2 to 5, 10, 15, or 20 mM per day,        e.g., a concentration of the dissolved salt administered by a        loading bolus dose of about 4 to 8 or 9 mM per day) and then an        IV infusion over 24 hours for 3 days (e.g., at a rate of 1, 2,        3, 5, 6, 7, 8, 10, 15, 20, 25, 30, or 50 mg/hr for 24 hours,        e.g., at a rate of 3, 6, or 15 mg/hr).    -   1.105 Composition 1.103 wherein the composition is for injection        intramuscularly, e.g., IM bolus and/or IM infusion, e.g., IM        bolus followed by IM infusion.    -   1.106 Composition 1.104 or 1.105 wherein the infusion, e.g., IV        or IM, is administered over about 10 or 30 minutes to 72 hours,        e.g., about 30 minutes to 24 hours, e.g, about 30 minutes to 12        hours, e.g., about 30 minutes to 8 hours, e.g., about 30 minutes        to 6 hours, e.g., about 30 minutes to 4 hours, e.g., about 30        minutes to 2 hours, e.g., about 30 minutes to 1 hour, e.g.,        about 72 hours.    -   1.107 Composition 1.2-1.106 wherein the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and the one or more bases are milled        together.    -   1.108 Composition I wherein the composition is formulated for        oral administration.    -   1.109 Composition 1.108 wherein the composition is a tablet,        capsule, solution, suspension, or the like.    -   1.110 Composition I wherein the composition comprises between 20        and 500 mg        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate (Formula I), e.g., between about 25 and 450        mg, e.g., between about 30 and 400 mg, e.g., between about 35        and 350 mg, and one or more bases, e.g., one or more of        tris(hydroxymethyl)aminomethane, Na₂HPO₄, meglumine, and sodium        citrate, e.g., between 10 and 1500 mg of one or more of        tris(hydroxymethyl)aminomethane, Na₂HPO₄, meglumine, and sodium        citrate, e.g., between about 15 and 1000 mg, e.g., between about        20 and 600 mg, e.g., between about 50 and 200 mg, e.g., between        about 50 and 150 mg, e.g., between 10 and 1500 mg of the base,        e.g., between about 15 and 1000 mg, e.g., between about 20 and        600 mg, e.g., between about 50 and 200 mg, e.g., between about        50 and 150 mg.    -   1.111 Composition 1.110 wherein the composition comprises        between 20 and 500 mg        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate (Formula I), e.g., between about 25 and 450        mg, e.g., between about 30 and 400 mg, e.g., between about 35        and 350 mg, and tris(hydroxymethyl)aminomethane, e.g., between        10 and 600 mg tris(hydroxymethyl)aminomethane, e.g., between        about 20 and 500, e.g., between about 40 and 500 mg.    -   1.112 Composition 1.110 wherein the composition comprises        between 20 and 500 mg        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate (Formula I), e.g., between about 25 and 450        mg, e.g., between about 30 and 400 mg, e.g., between about 35        and 350 mg, and Na₂HPO₄, e.g., between 10 and 600 mg Na₂HPO₄,        e.g., between about 20 and 500, e.g., between about 40 and 500        mg.    -   1.113 Composition 1.110 wherein the composition comprises        between 20 and 500 mg        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate (Formula I), e.g., between about 25 and 450        mg, e.g., between about 30 and 400 mg, e.g., between about 35        and 350 mg, and meglumine, e.g., between 20 and 900 mg        meglumine, e.g., between about 30 and 800, e.g., between about        60 and 500 mg, e.g, between about 70 and 400 mg.    -   1.114 Composition 1.110 wherein the composition comprises        between 20 and 500 mg        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate (Formula I), e.g., between about 25 and 450        mg, e.g., between about 30 and 400 mg, e.g., between about 35        and 350 mg, and sodium citrate, e.g., between 30 and 1500 mg        sodium citrate, e.g., between about 40 and 1200, e.g., between        about 50 and 1000 mg, e.g, between about 80 and 600 mg, e.g.,        between about 100 and 500 mg.    -   1.115 Composition 1.110-1.114 wherein the composition is admixed        with a solvent, e.g., sterile water for injection, a sterile        solution comprising dextrose (e.g., dextrose injection 5%), a        sterile solution comprising sodium chloride (e.g., 0.9% sodium        chloride injection), a sterile solution comprising benzyl        alcohol (e.g., bacteriostatic water for injection with benzyl        alcohol or bacteriostatic sodium chloride for injection with        benzyl alcohol), or Lactated Ringer's, e.g., wherein the        composition is admixed with 1 mL to 100 mL, e.g., about 3 to 50        mL, e.g., about 3.5 to 35 mL.    -   1.116 Composition 1.110-1.115 wherein the composition is admixed        with a sterile water for injection, e.g., wherein the        composition is admixed with 1 mL to 100 mL, e.g., about 3 to 50        mL, e.g., about 3.5 to 35 mL.    -   1.117 Composition 1.110-1.115 wherein the composition is admixed        with a sterile solution comprising sodium chloride (e.g., 0.9%        sodium chloride injection), e.g., wherein the composition is        admixed with 1 mL to 100 mL, e.g., about 3 to 50 mL, e.g., about        3.5 to 35 mL.    -   1.118 Composition I or 1.1-1.117 wherein the composition        comprises one or more additional therapeutic agents, e.g., one        or more additional therapeutic agents for cerebral edema,        stroke, traumatic brain injury, glioma (e.g., glioblastoma),        meningitis, acute mountain sickness, infection, metabolic        disorder, hypoxia, water intoxication, hepatic failure, hepatic        encephalopathy, diabetic ketoacidosis, abscess, eclampsia,        Creutzfeldt-Jakob disease, lupus cerebritis, optic nerve edema,        hyponatremia, fluid retention, ovarian hyperstimulation        syndrome, epilepsy, retinal ischemia or other diseases of the        eye associated with abnormalities in intraocular pressure and/or        tissue hydration, myocardial ischemia, myocardial        ischemia/reperfusion injury, myocardial infarction, myocardial        hypoxia, congestive heart failure, sepsis, neuromyelitis optica,        or migraines.    -   1.119 Composition I or 1.1-1.118 wherein the composition        comprises one or more additional therapeutic agents, e.g., one        or more additional therapeutic agents for pulmonary edema,        fibromyalgia, or multiple sclerosis.    -   1.120 Composition I or 1.1-1.119 wherein the composition is        stable for at least one week at room temperature, e.g., for at        least 1, 2, 4, 6, 8, or 12 months, e.g., the composition has        <20%        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        <15%        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        <10%        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        <5%        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        <2%        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        1%        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        or <1%        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide.    -   1.121 Composition I or 1.1-1.120 wherein the composition        comprises less than 10%, 150%, or 20% of        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        e.g., less than 5, 4, 3, or 2% of        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide        for at least one week, e.g., for at least 1, 2, 4, 6, 8, or 12        months.    -   1.122 Composition I or 1.1-1.121 wherein the composition is        administered concurrently or sequentially, in either order, with        one or more additional therapeutic agents, e.g., one or more        additional therapeutic agents for cerebral edema, stroke,        traumatic brain injury, glioma (e.g., glioblastoma), meningitis,        acute mountain sickness, infection, metabolic disorder, hypoxia,        water intoxication, hepatic failure, hepatic encephalopathy,        diabetic ketoacidosis, abscess, eclampsia, Creutzfeldt-Jakob        disease, lupus cerebritis, optic nerve edema, hyponatremia,        fluid retention, ovarian hyperstimulation syndrome, epilepsy,        retinal ischemia or other diseases of the eye associated with        abnormalities in intraocular pressure and/or tissue hydration,        myocardial ischemia, myocardial ischemia/reperfusion injury,        myocardial infarction, myocardial hypoxia, congestive heart        failure, sepsis, neuromyelitis optica, or migraines.    -   1.123 Composition I or 1.1-1.122 wherein the composition is        administered concurrently or sequentially, in either order, with        one or more additional therapeutic agents, e.g., one or more        additional therapeutic agents for pulmonary edema, fibromyalgia,        or multiple sclerosis.    -   1.124 Composition I or 1.1-1.123 wherein the composition is for        use in any of the methods described herein, e.g., for use in        Method A, e.g., Method A.1-A.58, for use in Method B, e.g.,        Method B.1-B.41, e.g., for use in Method C, e.g., C.1-C.8, e.g.,        for use in Method D, e.g., D.1-D.19, e.g., for use in Method E,        e.g., E.1-E.59, e.g., for use in Method F, e.g., F.1-F.5, e.g.,        for use in Method G, e.g., G.1-G.58, e.g., for use in Method H,        e.g., H.1-H.9, vida infra.

In some embodiments, when2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate, is provided as a solid that is to be admixed with a solvent,e.g., a sterile solution, to provide a pharmaceutically acceptableliquid, it is typically provided as a powder and admixed immediately orshortly before administration to the patient. In some embodiments, thepowdered 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyldihydrogen phosphate may be packaged in a container, for example, in avial to which is added the solvent, e.g., the sterile solution.Alternatively, the contents of the vial may be added to the solvent,e.g., the sterile solution, in a separate container. In someembodiments, the powdered2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is packaged in a sachet, such as a foil package, that can beopened and the contents added to the solvent, e.g., the sterilesolution. In some embodiments, the powdered2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is formulated as a tablet that dissolves when it is added tothe solvent, e.g., the sterile solution.

In yet another embodiment, a pharmaceutical composition comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate, e.g., Composition I, e.g., composition 1.1-1.124, is preparedby admixing 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyldihydrogen phosphate with a pharmaceutically acceptable excipient. Insome embodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate and the pharmaceutically acceptable excipient are milledtogether. In some embodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is crystalline. In some embodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is amorphous. In some embodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is lyophilized. In some embodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate and the pharmaceutically acceptable excipient, e.g.,Composition I, e.g., composition 1.1-1.124, are lyophilized.

In yet another embodiment, a pharmaceutical composition comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate, e.g., Composition I, e.g., composition 1.1-1.124, is preparedby admixing 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyldihydrogen phosphate with a sterile solution, e.g., sterile water forinjection or a sterile solution comprising sodium chloride (e.g., 0.9%sodium chloride injection), to form a pharmaceutically acceptableliquid. In some embodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is admixed with the sterile solution immediately or shortlybefore administration. In some embodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is admixed with a base, e.g., sodium citrate, sodium phosphate(e.g., Na₂HPO₄), tris(hydroxymethyl)aminomethane, and/or atris(hydroxymethyl)aminomethane salt (e.g., tris acetate) prior toadmixture with the sterile solution, e.g., sterile water for injectionor a sterile solution comprising sodium chloride (e.g., 0.9% sodiumchloride injection). In some embodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is admixed with a base, e.g., sodium citrate, sodium phosphate(e.g., Na₂HPO₄), tris(hydroxymethyl)aminomethane, and/or atris(hydroxymethyl)aminomethane salt (e.g., tris acetate) and/or abulking agent, e.g., dextran (e.g., dextran 40), prior to admixture withthe sterile solution, e.g., sterile water for injection or a sterilesolution comprising sodium chloride (e.g., 0.9% sodium chlorideinjection). In some embodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate admixed with the base and/or the bulking agent is lyophilized.In some embodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate admixed with the base and/or the bulking agent are milledtogether. In some embodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is admixed with a sterile solution comprising a base, e.g.,sodium citrate, sodium phosphate (e.g., Na₂HPO₄),tris(hydroxymethyl)aminomethane, and/or atris(hydroxymethyl)aminomethane salt (e.g., tris acetate). In someembodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is admixed with a sterile solution comprising a base, e.g.,sodium citrate, sodium phosphate (e.g., Na₂HPO₄),tris(hydroxymethyl)aminomethane base, and/or atris(hydroxymethyl)aminomethane salt (e.g.,tris(hydroxymethyl)aminomethane acetate) and/or a bulking agent. In someembodiments, the admixture of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate and the sterile solution is agitated, e.g., any mode ofagitation that results in a clear liquid, e.g., mechanical agitation,sonication, conventional mixing, conventional stirring and thecombinations thereof. In some embodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate admixed with the sterile solution is lyophilized. In someembodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate admixed with the sterile solution is crystalline. In someembodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate admixed with the sterile solution is amorphous.

In one embodiment, Composition 1, e.g., composition 1.1-1.124, isprepared by admixing2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate with a solvent, e.g., a sterile water for injection or asterile solution comprising sodium chloride (e.g., 0.9% sodium chlorideinjection). In some embodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is admixed with a base, e.g., sodium citrate, sodium phosphate(e.g., Na₂HPO₄), tris(hydroxymethyl)aminomethane, and/or atris(hydroxymethyl)aminomethane salt (e.g.,tris(hydroxymethyl)aminomethane acetate) and/or a bulking agent, e.g.,dextran (e.g., dextran 40), prior to admixture with the solvent, e.g. anaqueous solution. In some embodiments, the solvent, e.g., the aqueoussolution, comprises a base, e.g., sodium citrate, sodium phosphate(e.g., Na₂HPO₄), tris(hydroxymethyl)aminomethane, and/or atris(hydroxymethyl)aminomethane salt (e.g.,tris(hydroxymethyl)aminomethane acetate) and/or a bulking agent, e.g.,dextran (e.g., dextran 40). In some embodiments, the admixture of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate and the solvent, e.g., the aqueous solution, is agitated afteradmixture, e.g., by any mode of agitation that results in a clearliquid, e.g., mechanical agitation, sonication, conventional mixing,conventional stirring and the combinations thereof. In some embodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is lyophilized. In some embodiments, the admixture of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate and the base and/or bulking agent is lyophilized. In someembodiments, the admixture of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate and the base and/or bulking agent is milled together. In someembodiments,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is admixed with the solvent, e.g., the sterile solution,immediately or shortly before administration.

Pharmaceutical compositions disclosed herein, e.g., Composition I, e.g.,composition 1.1-1.124, may be contained in a sterilized vessel such assyringes, vials or ampoules of various sizes and capacities.

The pH of the pharmaceutical compositions disclosed herein whendissolved in solvent, e.g., an aqueous solution, e.g., Composition I,e.g., composition 1.1-1.124, may be adjusted to achieve the desired pHby addition of a metal hydroxide salt (e.g., NaOH and/or KOH, e.g.,NaOH) to the composition.

In some embodiments, the base is a solid.

The bases used herein may form a buffer with the2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate. If a solution of the base described herein andbis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate is too basic, the phosphate group may be cleaved. On the otherhand, if the solution is too acidic, the solubility of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate may decrease.

In some embodiments, “base” is any inorganic or organic Bronsted base.

Further provided is a method for increasing the stability of a solidstate formulation comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate, wherein the method comprises milling2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate with a base, e.g., with tris(hydroxymethyl)aminomethane forlater reconstitution as an aqueous solution for injection.

Further provided is a method for lessening the potential forprecipitation ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide andallows for IV administration comprising comprises milling2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate with a base, e.g., with tris(hydroxymethyl)aminomethane andreconstituting as an aqueous solution for injection.

Further provided is a method for increasing the aqueous solubility,dissolution and bioavailability ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamidecomprising preparing Formula II

by reacting a compound of Formula I

with a free base, e.g., tris(hydroxymethyl)aminomethane, e.g.,meglumine.

Further provided is a method for increasing the aqueous solubility,dissolution and bioavailability ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamidecomprising preparing Formula III

by reacting a compound of Formula I

with a free base, e.g., tris(hydroxymethyl)aminomethane, e.g.,meglumine.

Further provided is a method (Method I) of making a pharmaceuticalcomposition comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate, e.g., Composition I, e.g., composition 1.1-1.124, wherein themethod comprises admixing2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate and a pharmaceutically acceptable excipient.

Further provided is Method I as follows:

-   -   1.1 Method I wherein the pharmaceutically acceptable excipient        comprises one or more bases.    -   1.2 Method I or 1.1 comprising admixing 0.1 or 0.25 mg to 2.0 g        of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate, e.g., from about 0.1 or 0.25 mg to 75 or        600 mg, e.g., from about 0.1 or 0.25 or 1 or 2 or 5 or 10 or 15        or 20 mg to 50, 75, 100, 125, 150, 200, 300, 350, 400, 500, or        600 mg, or 1 g, 1.5 g, or 2.0 g, e.g., from about 5 to 50, 75,        100, 125, 150, 200, 300, 350, 400, 500, or 600 mg, or 1 g, 1.5        g, or 2 g, e.g., from about 5 to 500 mg, e.g., from about 5 to        300 or 350 mg, e.g., from about 5 to 200 mg, e.g., from about 25        to 500 mg, e.g., from about 25 to 300 or 350 mg, e.g., from        about 25 to 200 mg, e.g., from about 15, 20, 30, 35, 50 or 100        to 150, 200, 300, 350, 400, 450, 500, 550, or 600 mg, e.g., from        about 0.5 or 1 mg to 50 mg, e.g., from about 0.5 or 1 mg to 20        mg, e.g., from about 0.5 or 1 mg to 10 mg, e.g., from about 1 or        2 or 5 mg to 10 or 20 mg, e.g., from about 1 or 2 or 3 or 4 to 5        mg, e.g., about 35 mg, e.g., about 350 mg, or wherein the        composition admixing an amount of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate sufficient to provide 0.1 or 0.25 mg to 2.0        g of        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        e.g., from about 0.1 or 0.25 mg to 75 or 600 mg, e.g., from        about 0.1 or 0.25 or 1 or 2 or 5 or 10 or 15 or 20 mg to 50, 75,        100, 125, 150, 200, 300, 350, 400, 500, or 600 mg, or 1 g, 1.5        g, or 2.0 g, e.g., from about 5 to 50, 75, 100, 125, 150, 200,        300, 350, 400, 500, or 600 mg, or 1 g, 1.5 g, or 2 g, e.g., from        about 5 to 500 mg, e.g., from about 5 to 300 or 350 mg, e.g.,        from about 5 to 200 mg, e.g., from about 25 to 500 mg, e.g.,        from about 25 to 300 or 350 mg, e.g., from about 25 to 200 mg,        e.g., from about 15, 20, 30, 35, 50 or 100 to 150, 200, 300,        350, 400, 450, 500, 550, or 600 mg, e.g., from about 0.5 or 1 mg        to 50 mg, e.g., from about 0.5 or 1 mg to 20 mg, e.g., from        about 0.5 or 1 mg to 10 mg, e.g., from about 1 or 2 or 5 mg to        10 or 20 mg, e.g., from about 1 or 2 or 3 or 4 to 5 mg, e.g.,        about 35 mg, e.g., about 350 mg, with one or more bases.    -   1.3 Method I, 1.1 or 1.2 comprising admixing        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate in an amount sufficient to provide a dose        of 0.01 or 0.1 or 0.5 mg/kg to 1 or 5 or 10 or 15 mg/kg of        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        e.g., a dose of about 0.05 to 1 or 5 mg/kg, e.g., a dose of        about 0.05 to 0.1, 0.2, 0.3, 0.4, or 0.5 mg/kg with one or more        bases.    -   1.4 Method 1.1-1.3 wherein upon dissolution of the composition        in a solvent, e.g., the aqueous solution, the composition has a        pH between 7, 7.5, or 8 and 10.5, e.g., between about 7, 7.5, or        8 and 9.5, e.g., between about 7 or 7.5 and 8, e.g., between        about 7.5 and 8.5, e.g., about 7.5, e.g., about 8.5, e.g.,        between about 8 and 8.5, e.g., about 8.2, e.g., a base wherein a        conjugate acid of the base has a pKa between 6, 7, 8, 9, or 10        and 11, e.g., between about 6, 7, 8, or 9 and 10, e.g., between        about 7 and 9, e.g., between about 8 and 9, e.g., wherein the        one or more bases are one or more of:        -   a) a C₁₋₈-alkyl mono-, di-, or tri-carboxylic acid salt,            e.g., a citrate salt, e.g, a metal citrate salt (e.g., an            alkali and/or alkaline citrate salt, e.g., an alkali citrate            salt, e.g., sodium citrate and/or potassium citrate), e.g.,            a tartrate salt (e.g., a metal tartrate salt, an alkali            tartrate, e.g., sodium tartrate), e.g., a succinate salt            (e.g., a metal succinate salt, e.g., an alkali succinate,            e.g., disodium succinate), and/or e.g., a lactate salt            (e.g., a metal lactate salt, e.g., an alkali lactate, e.g.,            sodium lactate),        -   b) a phosphate salt, e.g., a metal phosphate salt (e.g., an            alkali and/or alkaline phosphate salt, e.g., an alkali            phosphate salt, e.g., sodium phosphate (e.g., NaH₂PO₄ and/or            Na₂HPO₄) and/or potassium phosphate (e.g., KH₂PO₄ and/or            K₂HPO₄)),        -   c) an amine and/or a salt thereof (e.g., morpholine, an            amino acid (e.g., arginine and/or lysine), a mono- and/or            poly-hydroxyalkylamine, and/or a salt thereof, e.g.,            (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a            salt thereof wherein each R⁸ is independently C₁₋₈alkyl            (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g.,            —CH₃) and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene,            e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g.,            one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and each n is            independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,            tris(hydroxymethyl)aminomethane (also known as tris base)            and/or a salt thereof (e.g., tris(hydroxymethyl)aminomethane            acetate (also known as tris acetate), meglumine,            dimethylethanolamine, diethylamine, diethylethanolamine,            and/or diethanolamine), e.g., any of the preceding wherein a            conjugate acid of the amine and/or salt thereof has a pKa            between 6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7,            8, or 9 and 10, e.g., between about 7 and 9, e.g., between            about 8 and 9,        -   d) a metal chloride salt (e.g., zinc chloride),        -   e) an acetate salt, e.g., a metal acetate salt (e.g., an            alkali and/or alkaline acetate salt, e.g., an alkali acetate            salt, e.g., sodium acetate and/or potassium acetate),        -   f) a hydroxide and/or alkoxide salt, e.g., a metal hydroxide            and/or alkoxide salt (e.g., a quarternary ammonium            hydroxide, e.g., ammonium hydroxide and/or choline            hydroxide, lithium hydroxide, aluminum hydroxide, e.g., an            alkali and/or alkaline hydroxide salt, e.g., sodium            hydroxide, potassium hydroxide, calcium hydroxide, magnesium            hydroxide, and/or magnesium ethoxide, e.g., sodium            hydroxide),        -   g) a carbonate and/or bicarbonate salt, e.g., a metal            carbonate and/or metal bicarbonate salt (e.g., an alkali            and/or alkaline carbonate salt, e.g., an alkali and/or            alkaline bicarbonate salt, e.g., sodium bicarbonate), and/or        -   h) a metal borate salt (e.g., an alkali borate salt, e.g.,            sodium borate),    -    e.g., one or more of sodium citrate, Na₂HPO₄,        tris(hydroxymethyl)aminomethane, and a        tris(hydroxymethyl)aminomethane salt (e.g., tris acetate), e.g.,        one or more of sodium citrate, Na₂HPO₄, and        tris(hydroxymethyl)aminomethane, e.g., one or more of sodium        citrate and Na₂HPO₄, e.g., Na₂HPO₄, e.g.,        tris(hydroxymethyl)aminomethane.    -   1.5 Method 1.1-1.4 wherein upon dissolution of the composition        in a solvent, e.g., the aqueous solution, the composition has a        pH between 7, 7.5, or 8 and 10.5, e.g., between about 7, 7.5, or        8 and 9.5, e.g., between about 7 or 7.5 and 8, e.g., between        about 7.5 and 8.5, e.g., about 7.5, e.g., about 8.5, e.g.,        between about 8 and 8.5, e.g., about 8.2, e.g., a base wherein a        conjugate acid of the base has a pKa between 6, 7, 8, 9, or 10        and 11, e.g., between about 6, 7, 8, or 9 and 10, e.g., between        about 7 and 9, e.g., between about 8 and 9, e.g., wherein the        one or more bases are one or more of:        -   a) a metal citrate salt (e.g., an alkali and/or alkaline            citrate salt, e.g., an alkali citrate salt, e.g., sodium            citrate and/or potassium citrate),        -   b) a metal phosphate salt (e.g., an alkali and/or alkaline            phosphate salt, e.g., an alkali phosphate salt, e.g., sodium            phosphate (e.g., NaH₂PO₄ and/or Na₂HPO₄) and/or potassium            phosphate (e.g., KH₂PO₄ and/or K₂HPO₄)),        -   c) an amine and/or a salt thereof (e.g., morpholine, an            amino acid (e.g., arginine), a mono- and/or            poly-hydroxyalkylamine, and/or a salt thereof, e.g.,            (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a            salt thereof wherein each R⁸ is independently C₁₋₈alkyl            (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g.,            —CH₃) and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene,            e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g.,            one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and each n is            independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,            tris(hydroxymethyl)aminomethane (also known as tris base)            and/or a salt thereof (e.g., tris(hydroxymethyl)aminomethane            acetate (also known as tris acetate), meglumine, and/or            diethanolamine), e.g., any of the preceding wherein a            conjugate acid of the amine and/or salt thereof has a pKa            between 6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7,            8, or 9 and 10, e.g., between about 7 and 9, e.g., between            about 8 and 9,        -   d) a metal acetate salt (e.g., an alkali and/or alkaline            acetate salt, e.g., an alkali acetate salt, e.g., sodium            acetate and/or potassium acetate),        -   e) a metal hydroxide salt (e.g., an alkali and/or alkaline            hydroxide salt, e.g., sodium hydroxide, potassium hydroxide,            calcium hydroxide, and/or magnesium hydroxide, e.g., sodium            hydroxide),        -   f) a metal carbonate and/or bicarbonate salt (e.g., an            alkali and/or alkaline carbonate salt, e.g., an alkali            and/or alkaline bicarbonate salt, e.g., sodium bicarbonate),            and/or        -   g) a metal borate salt (e.g., an alkali borate salt, e.g.,            sodium borate),    -    e.g., one or more of sodium citrate, Na₂HPO₄,        tris(hydroxymethyl)aminomethane, and a        tris(hydroxymethyl)aminomethane salt (e.g., tris acetate), e.g.,        one or more of sodium citrate, Na₂HPO₄, and        tris(hydroxymethyl)aminomethane, e.g., one or more of sodium        citrate and Na₂HPO₄, e.g., Na₂HPO₄, e.g.,        tris(hydroxymethyl)aminomethane.    -   1.6 Method 1.1-1.5 comprising admixing        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate with 1 or 5 mg to 200 or 500 mg of the one        or more bases, e.g., from about 1 or 5 or 10 mg to 15, 20, 25,        30, 40, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500,        1000, or 1500 mg, e.g., from about 15, 20, 30, 50, or 100 to        200, 250, 400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.7 Method 1.1-1.6 wherein the one or more bases comprise one or        more of a metal citrate salt (e.g., sodium citrate) and a metal        phosphate salt (e.g., sodium phosphate, e.g., Na₂HPO₄).    -   1.8 Method 1.1-1.7 wherein the one or more bases comprise a        metal citrate salt (e.g., sodium citrate).    -   1.9 Method 1.8 wherein the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is admixed with 1 or 5 mg to 200 or 500 mg        of a metal citrate salt (e.g., sodium citrate), e.g., from about        1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200,        250, 300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about        15, 20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700,        800, 1000, or 1500 mg.    -   1.10 Method 1.1-1.9 wherein the one or more bases comprise a        metal phosphate salt (e.g., sodium phosphate, e.g., Na₂HPO₄).    -   1.11 Method 1.10 wherein the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is admixed with 1 or 5 mg to 200 or 500 mg        of a metal phosphate salt (e.g., sodium phosphate, e.g.,        Na₂HPO₄), e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30,        40, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 1000,        or 1500 mg, e.g., from about 15, 20, 30, 50, or 100 to 200, 250,        400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.12 Method 1.1-1.11 wherein the one or more bases comprise        Na₂HPO₄.    -   1.13 Method 1.12 wherein the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is admixed with 1 or 5 mg to 200 or 500 mg        Na₂HPO₄, e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30, 40,        50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 1000, or        1500 mg, e.g., from about 15, 20, 30, 50, or 100 to 200, 250,        400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.14 Method 1.1-1.13 wherein the one or more bases comprise an        amine and/or a salt thereof (e.g., morpholine, an amino acid        (e.g., arginine), a mono- and/or poly-hydroxyalkylamine, and/or        a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]3N, and/or a salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        e.g., any of the preceding wherein a conjugate acid of the amine        and/or salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,        e.g., between about 6, 7, 8, or 9 and 10, e.g., between about 7        and 9, e.g., between about 8 and 9.    -   1.15 Method 1.14 wherein the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is admixed with 1 or 5 mg to 200 or 500 mg        of the amine and/or a salt thereof (e.g., morpholine, an amino        acid (e.g., arginine), a mono- and/or poly-hydroxyalkylamine,        and/or a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        e.g., any of the preceding wherein a conjugate acid of the amine        and/or salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,        e.g., between about 6, 7, 8, or 9 and 10, e.g., between about 7        and 9, e.g., between about 8 and 9, e.g., from about 1 or 5 or        10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300,        350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15, 20,        30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000,        or 1500 mg.    -   1.16 Method 1.1-1.15 wherein the one or more bases comprise a        mono- and/or poly-hydroxyalkylamine and/or a salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine).    -   1.17 Method 1.16 wherein the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is admixed with 1 or 5 mg to 200 or 500 mg        of the mono- and/or poly-hydroxyalkylamine and/or salt thereof,        e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a        salt thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., from about 1        or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250,        300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15,        20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800,        1000, or 1500 mg.    -   1.18 Method 1.1-1.17 wherein the one or more bases comprise        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine).    -   1.19 Method 1.18 wherein the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is admixed with 1 or 5 mg to 200 or 500 mg        of (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., from about 1        or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250,        300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15,        20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800,        1000, or 1500 mg.    -   1.20 Method 1.1-1.19 wherein the one or more bases comprise        tris(hydroxymethyl)aminomethane and/or meglumine, e.g.,        tris(hydroxymethyl)aminomethane, e.g., meglumine.    -   1.21 Method 1.20 wherein the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is admixed with 1 or 5 mg to 200 or 500 mg        tris(hydroxymethyl)aminomethane, e.g., from about 1 or 5 or 10        mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300, 350,        400, 450, 500, 1000, or 1500 mg, e.g., from about 15, 20, 30,        50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000, or        1500 mg and/or wherein the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is admixed with 1 or 5 mg to 200 or 500 mg        meglumine, e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30,        40, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 1000,        or 1500 mg, e.g., from about 15, 20, 30, 50, or 100 to 200, 250,        400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.22 Method 1.1-1.21 wherein the one or more bases comprise a        tris(hydroxymethyl)aminomethane salt, e.g.,        tris(hydroxymethyl)aminomethane acetate.    -   1.23 Method 1.22 wherein the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is admixed with 1 or 5 mg to 200 or 500 mg        of the tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate), e.g., from about 1 or        5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250,        300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15,        20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800,        1000, or 1500 mg, e.g., 1 or 5 mg to 200 or 500 mg        tris(hydroxymethyl)aminomethane acetate, e.g., from about 1 or 5        or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300,        350, 400, 450, 500, 1000, or 1500 mg        tris(hydroxymethyl)aminomethane acetate, e.g., from about 15,        20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800,        1000, or 1500 mg tris(hydroxymethyl)aminomethane acetate.    -   1.24 Method 1.1-1.23 wherein the one or more bases comprise a        base wherein a conjugate acid of the base has a pKa between 6,        7, 8, 9, or 10 and 11, e.g., between about 6, 7, 8, or 9 and 10,        e.g., between about 7 and 9, e.g., between about 8 and 9.    -   1.25 Method 1.24 wherein the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is admixed with 1 or 5 mg to 200 or 500 mg        of the base, e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30,        40, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 1000,        or 1500 mg, e.g., from about 15, 20, 30, 50, or 100 to 200, 250,        400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.26 Method 1.1-1.25 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the one or more bases is at least 1:1.    -   1.27 Method 1.1-1.26 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the one or more bases is at least 1:2,        e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.28 Method 1.27 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to a metal citrate salt (e.g., sodium        citrate) is at least 1:2, e.g., at least about 1:2, 1:3, 1:4, or        1:5 to 1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at        least about 1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20,        or 1:30, e.g., at least about 1:2.5, e.g., at least about 1:5,        e.g. at least about 1:10.    -   1.29 Method 1.27 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to a metal phosphate salt (e.g., sodium        phosphate, e.g., Na₂HPO₄) is at least 1:2, e.g., at least about        1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or        1:30, e.g., at least about 1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9,        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5, e.g., at        least about 1:5, e.g. at least about 1:10.    -   1.30 Method 1.27 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to an amine and/or salt thereof (e.g.,        morpholine, an amino acid (e.g., arginine), a mono- and/or        poly-hydroxyalkylamine, and/or salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., any of the        preceding wherein a conjugate acid of the amine and/or salt        thereof has a pKa between 6, 7, 8, 9, or 10 and 11, e.g.,        between about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9,        e.g., between about 8 and 9, is at least 1:2, e.g., at least        about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to 1:10, 1:15,        1:20, or 1:30, e.g., at least about 1:2.5 to 1:5, 1:6, 1:7, 1:8,        1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5,        e.g., at least about 1:5, e.g. at least about 1:10.    -   1.31 Method 1.27 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the mono- and/or poly-hydroxyalkylamine        and/or salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine)        is at least 1:2, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to        1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.32 Method 1.27 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C-s-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6)), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        e.g., any of the preceding wherein a conjugate acid of the amine        and/or salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,        e.g., between about 6, 7, 8, or 9 and 10, e.g., between about 7        and 9, e.g., between about 8 and 9, is 1:2, e.g., at least about        1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or        1:30, e.g., at least about 1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9,        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5, e.g., at        least about 1:5, e.g. at least about 1:10.    -   1.33 Method 1.27 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to tris(hydroxymethyl)aminomethane is at        least 1:2, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6,        1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.34 Method 1.27 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the tris(hydroxymethyl)aminomethane salt        (e.g., tris(hydroxymethyl)aminomethane acetate) is at least 1:2,        e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.35 Method 1.27 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to a base wherein a conjugate acid of the        base has a pKa between 6, 7, 8, 9, or 10 and 11, e.g., between        about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9, e.g.,        between about 8 and 9 is at least 1:2, e.g., at least about 1:2,        1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10,        1:15, 1:20, or 1:30, e.g., at least about 1:2.5, e.g., at least        about 1:5, e.g. at least about 1:10.    -   1.36 Method I or 1.1-1.35 further comprising admixing with one        or more bulking agents which may provide an adequate structure        to the lyophilized cake, e.g., one or more of mannitol, lactose,        sucrose, trehalose, sorbitol, glucose, raffinose, arginine,        glycine, histidine, dextran (e.g., dextran 40),        polyvinylpyrrolidone, polyethylene glycol, and polypropylene        glycol, e.g., one or more of mannitol, glucose, sucrose,        lactose, trehalose, and dextran (e.g., dextran 40).    -   1.37 Method I or 1.1-1.36 further comprising admixing with 5 or        10 or 50 mg to 2 or 5 g of one or more bulking agents, e.g.,        from about 50 or 100 mg to 200, 300, 500, or 800 mg, or 1, 1.5,        2, 3, 4, or 5 g of one or more bulking agents.    -   1.38 Method I or 1.1-1.37 further comprising admixing with        dextran (e.g., dextran 40).    -   1.39 Method I or 1.1-1.38 further comprising admixing with 5 or        10 or 50 mg to 2 or 5 g dextran (e.g., dextran 40), e.g., from        about 50 mg or 100 mg to 200, 300, 500, or 800 mg, or 1, 1.5, 2,        3, 4, or 5 g dextran (e.g., dextran 40).    -   1.40 Method I or 1.1-1.39 further comprising admixing with one        or more solubilizing agents, e.g., ethylenediamine tetraacetic        acid (EDTA) or a salt thereof (e.g., calcium disodium EDTA,        disodium EDTA, sodium EDTA), alpha cyclodextrin,        hydroxypropyl-β-cyclodextrin, polysorbate 80, tert-butanol,        isopropanol, dichloromethane, ethanol, acetone, and glycerol;        one or more collapse temperature modifiers which may shift the        overall collapse temperature higher, e.g., one or more of        dextran, Ficoll®, gelatin, and hydroxyethyl starch; one or more        tonicity modifiers, e.g., one or more of sodium chloride,        potassium chloride, sucrose, mannitol, glucose, and lactose; and        one or more antimicrobial agents, e.g., one or more of benzyl        alcohol, phenol, 2-phenoxyethanol, m-cresol, chlorobutanol,        parabens (e.g., methyl paraben, ethyl paraben, propyl paraben),        benzalkonium chloride, benzethonium chloride, myristyl        gamma-picolinium salt (e.g., myristyl gamma-picolinium        chloride), and organomercury compounds and salts (e.g., phenyl        mercuric acetate, phenyl mercuric borate, phenyl mercuric        nitrate, and thimerosal).    -   1.41 Method I or 1.1-1.40 further comprising milling the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and the one or more bases.    -   1.42 Method I or 1.1-1.41 further comprising lyophilizing the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and the one or more bases, e.g., by        freezing, primary drying, and secondary drying.    -   1.43 Method I or 1.1-1.42 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is lyophilized, e.g., by freezing, primary        drying, and secondary drying, prior to admixture with the        pharmaceutically acceptable excipient.    -   1.44 Method I or 1.1-1.43 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is crystalline.    -   1.45 Method I or 1.1-1.44 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is amorphous.    -   1.46 Method I or 1.1-1.45 further comprising constituting or        reconstituting, if lyophilized, the composition with a solvent,        e.g., the aqueous solution, into a pharmaceutically acceptable        liquid (e.g., a solution or suspension, e.g., a solution).    -   1.47 Method I or 1.1-1.46 further comprising admixing the        composition with a solvent, e.g., a sterile solution, e.g.,        sterile water for injection, a sterile solution comprising        dextrose (e.g., dextrose injection 5%), a sterile solution        comprising sodium chloride (e.g., 0.9% sodium chloride        injection), a sterile solution comprising benzyl alcohol (e.g.,        bacteriostatic water for injection with benzyl alcohol or        bacteriostatic sodium chloride for injection with benzyl        alcohol), or Lactated Ringer's.    -   1.48 Method I or 1.1-1.47 further comprising admixing the        composition with 0.5 to 500 mL solvent, e.g., an aqueous        solution, e.g., from about 1 or 2 mL to 500 mL, e.g., from about        1 or 2 mL to 5, 10, 25, 30, 35, 50, 75, 100, 150, 200, 300 or        500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 50, 75, 100, or        200 mL, e.g., from about 3.5 or 5 to 10, 25, 50, or 100 mL,        e.g., about 3.5 or 35 mL.    -   1.49 Method I or 1.1-1.48 further comprising admixing the        composition with 0.5 to 500 mL sterile solution, e.g., sterile        water for injection, a sterile solution comprising dextrose        (e.g., dextrose injection 5%), a sterile solution comprising        sodium chloride (e.g., 0.9% sodium chloride injection), a        sterile solution comprising benzyl alcohol (e.g., bacteriostatic        water for injection with benzyl alcohol or bacteriostatic sodium        chloride for injection with benzyl alcohol), or Lactated        Ringer's, e.g., from about 1 or 2 mL to 500 mL, e.g., from about        1 or 2 mL to 5, 10, 25, 30, 35, 50, 75, 100, 150, 200, 300 or        500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 50, 75, 100, or        200 mL, e.g., from about 3.5 or 5 to 10, 25, 50, or 100 mL,        e.g., about 3.5 or 35 mL.    -   1.50 Method I or 1.1-1.49 further comprising admixing the        composition with sterile water for injection or a sterile        solution comprising sodium chloride (e.g., 0.9% sodium chloride        injection).    -   1.51 Method I or 1.1-1.50 further comprising admixing the        composition with sterile water for injection.    -   1.52 Method 1.51 wherein the composition is admixed with 0.5 to        500 mL sterile water for injection, e.g., from about 1 or 2 mL        to 500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 30, 35, 50,        75, 100, 150, 200, 300 or 500 mL, e.g., from about 1 or 2 mL to        5, 10, 25, 50, 75, 100, or 200 mL, e.g., from about 3.5 or 5 to        10, 25, 50, or 100 mL, e.g., about 3.5 or 35 mL.    -   1.53 Method I or 1.1-1.52 further comprising admixing the        composition with a sterile solution comprising sodium chloride        (e.g., 0.9% sodium chloride injection).    -   1.54 Method 1.53 wherein the composition is admixed with 0.5 to        500 mL a sterile solution comprising sodium chloride (e.g., 0.9%        sodium chloride injection), e.g., from about 1 or 2 mL to 500        mL, e.g., from about 1 or 2 mL to 5, 10, 25, 30, 35, 50, 75,        100, 150, 200, 300 or 500 mL, e.g., from about 1 or 2 mL to 5,        10, 25, 50, 75, 100, or 200 mL, e.g., from about 3.5 or 5 to 10,        25, 50, or 100 mL, e.g., about 3.5 or 35 mL.    -   1.55 Method 1.47-1.54 wherein the composition comprises Formula        II

-   -   1.56 Method 1.47-1.55 wherein the composition comprises at least        a 1:1 molar ratio of Formula II to a cation of the base.    -   1.57 Method 1.47-1.54 wherein the composition comprises Formula        III

-   -   1.58 Method 1.47-1.54 or 1.57 wherein the composition comprises        at least a 1:2 molar ratio of Formula III to a cation of the        base e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8        to 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.59 Method 1.47-1.58 wherein the concentration of Formula II or        Formula III, e.g., the concentration of Formula II, e.g, the        concentration of Formula III, is 0.01 or 0.02 or 0.05 or 0.1 or        0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to        1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175,        200, 250 mM, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20,        25, 40, 50 or 60 mM, e.g., from about 5, 10, 15, 20, 25, or 50        to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20,        or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM.    -   1.60 Method 1.47-1.59 wherein the solvent, e.g., the sterile        solution, comprises a base, e.g., a base wherein upon        dissolution of the composition in the solvent, e.g., the sterile        solution, the composition has a pH between 7, 7.5, or 8 and        10.5, e.g., between about 7, 7.5, or 8 and 9.5, e.g., between        about 7 or 7.5 and 8, e.g., between about 7.5 and 8.5, e.g.,        about 7.5, e.g., about 8.5, e.g., between about 8 and 8.5, e.g.,        about 8.2, e.g., a base with a pKa between 6, 7, 8, 9, or 10 and        11, e.g., between about 6, 7, 8, or 9 and 10, e.g., between        about 7 and 9, e.g., between about 8 and 9 between 6 and 11,        e.g., between 6.5 and 10, e.g., between 7 and 9, e.g., wherein        the base is one or more of:        -   a) a C₁₋₈-alkyl mono-, di-, or tri-carboxylic acid salt,            e.g., a citrate salt, e.g, a metal citrate salt (e.g., an            alkali and/or alkaline citrate salt, e.g., an alkali citrate            salt, e.g., sodium citrate and/or potassium citrate), e.g.,            a tartrate salt (e.g., a metal tartrate salt, an alkali            tartrate, e.g., sodium tartrate), e.g., a succinate salt            (e.g., a metal succinate salt, e.g., an alkali succinate,            e.g., disodium succinate), and/or e.g., a lactate salt            (e.g., a metal lactate salt, e.g., an alkali lactate, e.g.,            sodium lactate),        -   b) a phosphate salt, e.g., a metal phosphate salt (e.g., an            alkali and/or alkaline phosphate salt, e.g., an alkali            phosphate salt, e.g., sodium phosphate (e.g., NaH₂PO₄ and/or            Na₂HPO₄) and/or potassium phosphate (e.g., KH₂PO₄ and/or            K₂HPO₄)),        -   a) an amine and/or a salt thereof (e.g., morpholine,            piperazine, benethamine, benzathine, trimethylglycine,            hydrabamine, 4-(2-hydroxyethyl)morpholine,            1-2-hydroxyethyl)-pyrrolidine, an amino acid (e.g., arginine            and/or lysine), a mono- and/or poly-hydroxyalkylamine,            and/or a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,            [(HO)_(n)R⁸]3N, and/or a salt thereof wherein each R⁸ is            independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,            e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene            (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—,            e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is            —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,            5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known            as tris base) and/or a salt thereof (e.g.,            tris(hydroxymethyl)aminomethane acetate (also known as tris            acetate), meglumine, dimethylethanolamine, diethylamine,            diethylethanolamine, and/or diethanolamine), e.g., any of            the preceding wherein a conjugate acid of the amine and/or            salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,            e.g., between about 6, 7, 8, or 9 and 10, e.g., between            about 7 and 9, e.g., between about 8 and 9,        -   b) a metal chloride salt (e.g., zinc chloride),        -   c) an acetate salt, e.g., a metal acetate salt (e.g., an            alkali and/or alkaline acetate salt, e.g., an alkali acetate            salt, e.g., sodium acetate and/or potassium acetate),        -   d) a hydroxide and/or alkoxide salt, e.g., a metal hydroxide            and/or alkoxide salt (e.g., a quarternary ammonium            hydroxide, e.g., ammonium hydroxide and/or choline            hydroxide, lithium hydroxide, aluminum hydroxide, e.g., an            alkali and/or alkaline hydroxide salt, e.g., sodium            hydroxide, potassium hydroxide, calcium hydroxide, magnesium            hydroxide, and/or magnesium ethoxide e.g., sodium            hydroxide),        -   e) a carbonate and/or bicarbonate salt, e.g., a metal            carbonate and/or metal bicarbonate salt (e.g., an alkali            and/or alkaline carbonate salt, e.g., an alkali and/or            alkaline bicarbonate salt, e.g., sodium bicarbonate), and/or        -   f) a metal borate salt (e.g., an alkali borate salt, e.g.,            sodium borate),    -    e.g., one or more of sodium citrate, Na₂HPO₄,        tris(hydroxymethyl)aminomethane, and a        tris(hydroxymethyl)aminomethane salt (e.g., tris acetate), e.g.,        one or more of sodium citrate, Na₂HPO₄, and        tris(hydroxymethyl)aminomethane, e.g., one or more of sodium        citrate and Na₂HPO₄, e.g., Na₂HPO₄, e.g.,        tris(hydroxymethyl)aminomethane.    -   1.61 Method 1.47-1.60 wherein the solvent, e.g., the sterile        solution, comprises a base, e.g., a base wherein upon        dissolution of the composition in the solvent, e.g., the sterile        solution, the composition has a pH between 7, 7.5, or 8 and        10.5, e.g., between about 7, 7.5, or 8 and 9.5, e.g., between        about 7 or 7.5 and 8, e.g., between about 7.5 and 8.5, e.g.,        about 7.5, e.g., about 8.5, e.g., between about 8 and 8.5, e.g.,        about 8.2, e.g., a base with a pKa between 6, 7, 8, 9, or 10 and        11, e.g., between about 6, 7, 8, or 9 and 10, e.g., between        about 7 and 9, e.g., between about 8 and 9, e.g., wherein the        base is one or more of:        -   a) a metal citrate salt (e.g., an alkali and/or alkaline            citrate salt, e.g., an alkali citrate salt, e.g., sodium            citrate and/or potassium citrate),        -   b) a metal phosphate salt (e.g., an alkali and/or alkaline            phosphate salt, e.g., an alkali phosphate salt, e.g., sodium            phosphate (e.g., NaH₂PO₄ and/or Na₂HPO₄) and/or potassium            phosphate (e.g., KH₂PO₄ and/or K₂HPO₄)),        -   c) an amine and/or a salt thereof (e.g., morpholine, an            amino acid (e.g., arginine), a mono- and/or            poly-hydroxyalkylamine, and/or a salt thereof, e.g.,            (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a            salt thereof wherein each R⁸ is independently C₁₋₈alkyl            (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g.,            —CH₃) and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene,            e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g.,            one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and each n is            independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,            tris(hydroxymethyl)aminomethane (also known as tris base)            and/or a salt thereof (e.g., tris(hydroxymethyl)aminomethane            acetate (also known as tris acetate), meglumine, and/or            diethanolamine), e.g., any of the preceding wherein a            conjugate acid of the amine and/or salt thereof has a pKa            between 6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7,            8, or 9 and 10, e.g., between about 7 and 9, e.g., between            about 8 and 9,        -   d) a metal acetate salt (e.g., an alkali and/or alkaline            acetate salt, e.g., an alkali acetate salt, e.g., sodium            acetate and/or potassium acetate),        -   e) a metal hydroxide salt (e.g., an alkali and/or alkaline            hydroxide salt, e.g., sodium hydroxide, potassium hydroxide,            calcium hydroxide, and/or magnesium hydroxide, e.g., sodium            hydroxide),        -   f) a metal carbonate and/or bicarbonate salt (e.g., an            alkali and/or alkaline carbonate salt, e.g., an alkali            and/or alkaline bicarbonate salt, e.g., sodium bicarbonate),            and/or        -   g) a metal borate salt (e.g., an alkali borate salt, e.g.,            sodium borate),    -    e.g., one or more of sodium citrate, Na₂HPO₄,        tris(hydroxymethyl)aminomethane, and a        tris(hydroxymethyl)aminomethane salt (e.g., tris acetate), e.g.,        one or more of sodium citrate, Na₂HPO₄, and        tris(hydroxymethyl)aminomethane, e.g., one or more of sodium        citrate and Na₂HPO₄, e.g., Na₂HPO₄, e.g.,        tris(hydroxymethyl)aminomethane.    -   1.62 Method 1.61 wherein the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and the base, e.g., sodium citrate, sodium        phosphate (e.g., Na₂HPO₄), tris(hydroxymethyl)aminomethane,        and/or a tris(hydroxymethyl)aminomethane salt (e.g., tris        acetate), form a salt.    -   1.63 Method 1.60-1.62 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of the one or        more base, e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30,        40, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 1000,        or 1500 mg, e.g., from about 15, 20, 30, 50, or 100 to 200, 250,        400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.64 Method 1.60-1.63 wherein the concentration of each of the        one or more bases is 0.01 or 0.02 or 0.05 or 0.1 or 0.5 or 1 or        2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to 1, 2, 5, 10,        15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175, 200, 250, or        1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25, 40, 50 or 60        mM, e.g., from about 5, 10, 15, 20, 25, or 50 to 100, 200, 250,        300, 400, 500, or 1000 mM, e.g., about 2, 20, or 200 mM, e.g.,        about 5, 10, 50, 500, 500, or 1000 mM, e.g., from about 5, 10,        15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM,        e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500,        or 1000 mM, e.g., wherein the concentration of each of the one        or more bases is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of        Formula II, e.g., about 2.5 or 5 to 10, e.g. about 2.5, e.g.,        about 5, e.g., wherein the concentration of each of the one or        more bases is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of        Formula III, e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.65 Method 1.60-1.64 wherein the one or more bases comprise one        or more of a metal citrate salt (e.g., sodium citrate) and a        metal phosphate salt (e.g., sodium phosphate, e.g., Na₂HPO₄).    -   1.66 Method 1.60-1.65 wherein the one or more bases comprise a        metal citrate salt (e.g., sodium citrate).    -   1.67 Method 1.66 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of a metal        citrate salt (e.g., sodium citrate), e.g., from about 1 or 5 or        10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300,        350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15, 20,        30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000,        or 1500 mg.    -   1.68 Method 1.67 wherein the concentration of the metal citrate        salt (e.g., sodium citrate) is 0.01 or 0.02 or 0.05 or 0.1 or        0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to        1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175,        200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25,        40, 50 or 60 mM, e.g., from about 5, 10, 15, 20, 25, or 50 to        100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20, or        200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g., from        about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500,        or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., wherein the concentration of the        metal citrate salt is 2 or 3 to 5, 6, 8, 10, 15 or 20        equivalents of Formula II, e.g., about 2.5 or 5 to 10, e.g.        about 2.5, e.g., about 5, e.g., wherein the concentration of the        metal citrate salt is 2 or 3 to 5, 6, 8, 10, 15 or 20        equivalents of Formula III, e.g., about 5 to 10, e.g. about 5,        e.g., about 10.    -   1.69 Method 1.60-1.68 wherein the one or more bases comprise        metal phosphate salt (e.g., sodium phosphate, e.g., Na₂HPO₄).    -   1.70 Method 1.69 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of a metal        phosphate salt (e.g, sodium phosphate, e.g., Na₂HPO₄), e.g.,        from about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100,        150, 200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg, e.g.,        from about 15, 20, 30, 50, or 100 to 200, 250, 400, 450, 500,        600, 700, 800, 1000, or 1500 mg.    -   1.71 Method 1.70 wherein the concentration of the metal        phosphate salt (e.g., sodium phosphate, e.g., Na₂HPO₄), is 0.01        or 0.02 or 0.05 or 0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from        about 0.01 or 0.1 or 0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60,        75, 100, 125, 150, 175, 200, 250, or 1000 mM, e.g. from about 1        to 2, 5, 10, 15, 20, 25, 40, 50 or 60 mM, e.g., from about 5,        10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500, or 1000        mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50, 500,        500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50 to        100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20, or        200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of the metal phosphate salt (e.g.,        sodium phosphate, e.g., Na₂HPO₄) is 2 or 3 to 5, 6, 8, 10, 15 or        20 equivalents of Formula II, e.g., about 2.5 or 5 to 10, e.g.        about 2.5, e.g., about 5, e.g., wherein the concentration of the        metal phosphate salt (e.g., sodium phosphate, e.g., Na₂HPO₄) is        2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula III,        e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.72 Method 1.60-1.71 wherein the one or more bases comprise an        amine and/or a salt thereof (e.g., morpholine, an amino acid        (e.g., arginine), a mono- and/or poly-hydroxyalkylamine, and/or        a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        e.g., any of the preceding wherein a conjugate acid of the amine        and/or salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,        e.g., between about 6, 7, 8, or 9 and 10, e.g., between about 7        and 9, e.g., between about 8 and 9.    -   1.73 Method 1.72 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of the amine        and/or a salt thereof (e.g., morpholine, an amino acid (e.g.,        arginine), a mono- and/or poly-hydroxyalkylamine, and/or a salt        thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N,        and/or a salt thereof wherein each R⁸ is independently C₁₋₈alkyl        (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃)        and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g.,        C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is        —CH₃ and another R⁸ is —(CH₂)₆—) and each n is independently 1-8        (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        e.g., any of the preceding wherein a conjugate acid of the amine        and/or salt thereof has a pKa between 6 and 11, e.g., between        6.5 and 10, e.g., between 7 and 9, e.g., from about 1 or 5 or 10        mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300, 350,        400, 450, 500, 1000, or 1500 mg, e.g., from about 15, 20, 30,        50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000, or        1500 mg.    -   1.74 Method 1.72 wherein the concentration of the amine and/or a        salt thereof (e.g., morpholine, an amino acid (e.g., arginine),        a mono- and/or poly-hydroxyalkylamine, and/or a salt thereof,        e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a        salt thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., any of the        preceding wherein a conjugate acid of the amine and/or salt        thereof has a pKa between 6, 7, 8, 9, or 10 and 11, e.g.,        between about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9,        e.g., between about 8 and 9, is 0.01 or 0.02 or 0.05 or 0.1 or        0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to        1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175,        200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25,        40, 50 or 60 mM, e.g., from about 5, 10, 15, 20, 25, or 50 to        100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20, or        200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g., from        about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500,        or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., wherein the concentration of the        amine and/or a salt thereof (e.g., morpholine, an amino acid        (e.g., arginine), a mono- and/or poly-hydroxyalkylamine, and/or        a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine)        is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula II,        e.g., about 2.5 or 5 to 10, e.g. about 2.5, e.g., about 5, e.g.,        wherein the concentration of the amine and/or a salt thereof        (e.g., morpholine, an amino acid (e.g., arginine), a mono-        and/or poly-hydroxyalkylamine, and/or a salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]3N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine) is 2 or 3 to 5, 6,        8, 10, 15 or 20 equivalents of Formula III, e.g., about 5 to 10,        e.g. about 5, e.g., about 10.    -   1.75 Method 1.60-1.74 wherein the one or more bases comprise a        mono- and/or poly-hydroxyalkylamine and/or a salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine).    -   1.76 Method 1.75 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of the mono-        and/or poly-hydroxyalkylamine and/or salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., from about 1        or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250,        300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15,        20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800,        1000, or 1500 mg.    -   1.77 Method 1.76 wherein the concentration of the mono- and/or        poly-hydroxyalkylamine and/or salt thereof, e.g., (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or salt thereof wherein        each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), is 0.01 or 0.02 or        0.05 or 0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or        0.1 or 0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125,        150, 175, 200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10,        15, 20, 25, 40, 50 or 60 mM, e.g., from about 5, 10, 15, 20, 25,        or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about        2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM,        e.g., from about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300,        400, 500, or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about        5, 10, 50, 500, 500, or 1000 mM, e.g., wherein the concentration        of the mono- and/or poly-hydroxyalkylamine and/or salt thereof,        e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or        salt thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine) is 2 or 3 to 5, 6,        8, 10, 15 or 20 equivalents of Formula II, e.g., about 2.5 or 5        to 10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of each of the mono- and/or poly-hydroxyalkylamine        and/or salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine)        is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula III,        e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.78 Method 1.60-1.77 wherein the one or more bases comprise        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine).    -   1.79 Method 1.78 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of (HO)_(n)R⁸NH₂,        [(HO)₁R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each        R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., from about 1        or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250,        300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15,        20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800,        1000, or 1500 mg.    -   1.80 Method 1.78 wherein the concentration of (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]3N, and/or a salt thereof wherein        each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), is 0.01 or 0.02 or        0.05 or 0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or        0.1 or 0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125,        150, 175, 200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10,        15, 20, 25, 40, 50 or 60 mM, e.g., from about 5, 10, 15, 20, 25,        or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about        2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM,        e.g., from about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300,        400, 500, or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about        5, 10, 50, 500, 500, or 1000 mM, e.g., wherein the concentration        of (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine) is 2 or 3 to 5, 6,        8, 10, 15 or 20 equivalents of Formula II, e.g., about 2.5 or 5        to 10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N,        and/or a salt thereof wherein each R⁸ is independently C₁₋₈alkyl        (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃)        and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g.,        C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is        —CH₃ and another R⁸ is —(CH₂)₆—) and each n is independently 1-8        (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine)        is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula III,        e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.81 Method 1.60-1.80 wherein the one or more bases comprise        tris(hydroxymethyl)aminomethane and/or meglumine, e.g.,        tris(hydroxymethyl)aminomethane, e.g, meglumine.    -   1.82 Method 1.81 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of        tris(hydroxymethyl)aminomethane, e.g., from about 1 or 5 or 10        mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300, 350,        400, 450, 500, 1000, or 1500 mg, e.g., from about 15, 20, 30,        50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000, or        1500 mg and/or wherein the solvent, e.g., the sterile solution,        comprises 1 or 5 mg to 200 or 500 mg of meglumine, e.g., from        about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150,        200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from        about 15, 20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600,        700, 800, 1000, or 1500 mg.    -   1.83 Method 1.81 wherein the concentration of        tris(hydroxymethyl)aminomethane is 0.01 or 0.02 or 0.05 or 0.1        or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5        to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175,        200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25,        40, 50 or 60 mM, e.g., from about 5, 10, 15, 20, 25, or 50 to        100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20, or        200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g., from        about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500,        or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., wherein the concentration of        tris(hydroxymethyl)aminomethane is 2 or 3 to 5, 6, 8, 10, 15 or        20 equivalents of Formula II, e.g., about 2.5 or 5 to 10, e.g.        about 2.5, e.g., about 5, e.g., wherein the concentration of        tris(hydroxymethyl)aminomethane is 2 or 3 to 5, 6, 8, 10, 15 or        20 equivalents of Formula III, e.g., about 5 to 10, e.g. about        5, e.g., about 10 and/or wherein the concentration of meglumine        is 0.01 or 0.02 or 0.05 or 0.1 or 0.5 or 1 or 2 to 250 mM, e.g.,        from about 0.01 or 0.1 or 0.5 to 1, 2, 5, 10, 15, 20, 25, 40,        50, 60, 75, 100, 125, 150, 175, 200, 250, or 1000 mM, e.g. from        about 1 to 2, 5, 10, 15, 20, 25, 40, 50 or 60 mM, e.g., from        about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500,        or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50        to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20,        or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of meglumine is 2 or 3 to 5, 6, 8, 10,        15 or 20 equivalents of Formula II, e.g., about 2.5 or 5 to 10,        e.g. about 2.5, e.g., about 5, e.g., wherein the concentration        of meglumine is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of        Formula III, e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.84 Method 1.60-1.83 wherein the one or more bases comprise a        tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate).    -   1.85 Method 1.84 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of the        tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate), e.g., from about 1 or        5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250,        300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15,        20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800,        1000, or 1500 mg.    -   1.86 Method 1.84 wherein the concentration of the        tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate) is 0.01 or 0.02 or 0.05        or 0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1        or 0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125,        150, 175, 200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10,        15, 20, 25, 40, 50 or 60 mM, e.g., from about 5, 10, 15, 20, 25,        or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about        2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM.    -   1.87 Method 1.60-1.86 wherein the one or more bases comprise a        base wherein a conjugate acid of the base has a pKa between 6,        7, 8, 9, or 10 and 11, e.g., between about 6, 7, 8, or 9 and 10,        e.g., between about 7 and 9, e.g., between about 8 and 9.    -   1.88 Method 1.87 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of the base,        e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75,        100, 150, 200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg,        e.g., from about 15, 20, 30, 50, or 100 to 200, 250, 400, 450,        500, 600, 700, 800, 1000, or 1500 mg.    -   1.89 Method 1.87 wherein the concentration of the base is 0.01        or 0.02 or 0.05 or 0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from        about 0.01 or 0.1 or 0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60,        75, 100, 125, 150, 175, 200, 250, or 1000 mM, e.g. from about 1        to 2, 5, 10, 15, 20, 25, 40, 50 or 60 mM, e.g., from about 5,        10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500, or 1000        mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50, 500,        500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50 to        100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20, or        200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of the base is 2 or 3 to 5, 6, 8, 10,        15 or 20 equivalents of Formula II, e.g., about 2.5 or 5 to 10,        e.g. about 2.5, e.g., about 5, e.g., wherein the concentration        of the base is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of        Formula III, e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.90 Method 1.47-1.89 wherein the solvent, e.g., the sterile        solution comprises one or more bulking agents, e.g., one or more        of maltose, mannose, ribose, cyclodextrin, mannitol, lactose,        sucrose, trehalose, sorbitol, glucose, raffinose, arginine,        glycine, histidine, dextran (e.g., dextran 40),        polyvinylpyrrolidone, polyethylene glycol, and polypropylene        glycol, e.g., one or more of mannitol, glucose, sucrose,        lactose, trehalose, and dextran (e.g., dextran 40).    -   1.91 Method 1.47-1.90 wherein the solvent, e.g., the sterile        solution, comprises 5 or 10 or 50 mg to 2 or 5 g of one or more        bulking agents, e.g., from about 50 or 100 mg to 200, 300, 500,        or 800 mg, or 1, 1.5, 2, 3, 4, or 5 g of one or more bulking        agents.    -   1.92 Method 1.47-1.91 wherein the solvent, e.g., the sterile        solution, comprises dextran (e.g., dextran 40).    -   1.93 Method 1.92 wherein the solvent, e.g. the sterile solution,        comprises 5 or 10 or 50 mg to 2 or 5 g dextran (e.g., dextran        40), e.g., from about 50 or 100 mg to 200, 300, 500, or 800 mg,        or 1, 1.5, 2, 3, 4, or 5 g dextran (e.g., dextran 40).    -   1.94 Method 1.47-1.93 wherein the solvent, e.g., the sterile        solution, comprises one or more solubilizing agents, e.g.,        ethylenediamine tetraacetic acid (EDTA) or a salt thereof (e.g.,        calcium disodium EDTA, disodium EDTA, sodium EDTA), alpha        cyclodextrin, hydroxypropyl-β-cyclodextrin, polysorbate 80,        tert-butanol, isopropanol, dichloromethane, ethanol, acetone,        and glycerol; one or more collapse temperature modifiers which        may shift the overall collapse temperature higher, e.g., one or        more of dextran, Ficoll®, gelatin, and hydroxyethyl starch; one        or more tonicity modifiers, e.g., one or more of sodium        chloride, potassium chloride, sucrose, mannitol, and glucose;        and one or more antimicrobial agents, e.g., one or more of        benzyl alcohol, phenol, 2-phenoxyethanol, m-cresol,        chlorobutanol, parabens (e.g., methyl paraben, ethyl paraben,        propyl paraben), benzalkonium chloride, benzethonium chloride,        myristyl gamma-picolinium salt (e.g., myristyl gamma-picolinium        chloride), and organomercury compounds and salts (e.g., phenyl        mercuric acetate, phenyl mercuric borate, phenyl mercuric        nitrate, and thimerosal).    -   1.95 Method 1.47-1.94 wherein the pH after admixture with the        solvent, e.g., an aqueous solution, is between pH 7 and pH 10.5,        e.g., between pH 7 and pH 9.5, e.g., between pH 7 and pH 8,        e.g., between 7.5 and 8.5, e.g., 7.5, e.g., 8.5, e.g., 8.2.    -   1.96 Method 1.47-1.95 wherein the pH after admixture with the        solvent, e.g., an aqueous solution, is further adjusted, e.g.,        adjusted to achieve a pH between pH 7 and pH 10.5, e.g., between        pH 7 and pH 9.5, e.g., between pH 7 and pH 8, e.g., between 7.5        and 8.5, e.g., 7.5, e.g., 8.5, e.g., 8.2, e.g., wherein the pH        is adjusted with NaOH.    -   1.97 Method 1.47-1.96 further comprising filtering after        admixture with the solvent, e.g., an aqueous solution, to remove        particles and microbes, e.g., filtered prior to injection.    -   1.98 Method 1.47-1.97 wherein the composition comprises Formula        II

-   -   1.99 Method 1.47-1.98 wherein the composition comprises at least        a 1:1 molar ratio of Formula II to a cation of the base.    -   1.100 Composition 1.47-1.96 wherein the composition comprises        Formula III

-   -   1.101 Method 1.47-1.96 or 1.100 wherein the composition        comprises at least a 1:2 ratio of Formula III to a cation of the        base, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7,        1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to        1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at        least about 1:2.5, e.g., at least about 1:5, e.g. at least about        1:10.    -   1.102 Method 1.47-1.101 wherein upon dissolution of the        composition in the solvent, e.g., the aqueous solution, the        composition has a pH between 7, 7.5, or 8 and 10.5, e.g.,        between about 7, 7.5, or 8 and 9.5, e.g., between about 7 or 7.5        and 8, e.g., between about 7.5 and 8.5, e.g., about 7.5, e.g.,        about 8.5, e.g., between about 8 and 8.5, e.g., about 8.2.    -   1.103 Method I or 1.1-1.102 further comprising admixing the        composition with one or more additional therapeutic agents,        e.g., one or more additional therapeutic agents for cerebral        edema, stroke, traumatic brain injury, glioma (e.g.,        glioblastoma), meningitis, acute mountain sickness, infection,        metabolic disorder, hypoxia, water intoxication, hepatic        failure, hepatic encephalopathy, diabetic ketoacidosis, abscess,        eclampsia, Creutzfeldt-Jakob disease, lupus cerebritis, optic        nerve edema, hyponatremia, fluid retention, ovarian        hyperstimulation syndrome, epilepsy, retinal ischemia or other        diseases of the eye associated with abnormalities in intraocular        pressure and/or tissue hydration, myocardial ischemia,        myocardial ischemia/reperfusion injury, myocardial infarction,        myocardial hypoxia, congestive heart failure, sepsis,        neuromyelitis optica, or migraines.    -   1.104 Method I or 1.1-1.103 further comprising admixing the        composition with one or more additional therapeutic agents,        e.g., one or more additional therapeutic agents for pulmonary        edema, fibromyalgia, or multiple sclerosis.

In yet another embodiment, provided is a salt solution (Salt Solution I)comprising a solvent, e.g., an aqueous solution, and a salt formed froma compound of Formula I

and an amine and/or a salt thereof (e.g., morpholine, piperazine,benethamine, benzathine, trimethylglycine, hydrabamine,4-(2-hydroxyethyl)morpholine, 1-(2 hydroxyethyl)-pyrrolidine, an aminoacid (e.g., arginine and/or lysine), a mono- and/orpoly-hydroxyalkylamine, and/or a salt thereof, e.g., (HO)_(n)R⁸NH₂,[(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each R⁸is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g.,—CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene,e.g., C₁₋₄-alkylene, e.g., CH₂CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is—CH₃ and another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane (also knownas tris base) and/or a salt thereof (e.g.,tris(hydroxymethyl)aminomethane acetate (also known as tris acetate),meglumine, dimethylethanolamine, diethylamine, diethylethanolamine,and/or diethanolamine), e.g., any of the preceding wherein a conjugateacid of the amine and/or salt thereof has a pKa between 6, 7, 8, 9, or10 and 11, e.g., between about 6, 7, 8, or 9 and 10, e.g., between about7 and 9, e.g., between about 8 and 9.

Further provided is Salt Solution I as follows:

-   -   1.1 Salt Solution I wherein the salt solution comprises Formula        II

-   -   1.2 Salt Solution I or 1.1 wherein the salt solution comprises        Formula III

1.3 Salt Solution I, 1.1, or 1.2 wherein the salt solution comprises aprotonated and/or unprotonated mono- and/or poly-hydroxyalkylamine,e.g., e.g., (HO)_(n)R⁸NH₃, [(HO)_(n)R⁸]₂NH₂, [(HO)_(n)R⁸]₃NH, e.g.,(HO)_(n)R⁸NH₃, [(HO)_(n)R⁸]₂NH₂, [(HO)_(n)R⁸]₃NH⁺, wherein each R⁸ isindependently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g.,—CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene,e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is—CH₃ and another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,1, 2, 3, 4, 5, or 6), e.g.,

-   -   1.4 Salt Solution I or 1.1-1.3 wherein the salt solution        comprises

-   -   1.5 Salt Solution I or 1.1-1.4 wherein the salt solution        comprises

-   -   1.6 Salt Solution I or 1.1-1.5 wherein the salt solution        comprises

-   -   1.7 Salt Solution I or 1.1-1.6 wherein the salt solution        comprises at least a 1:1 molar ratio of Formula II to the        protonated amine.    -   1.8 Salt Solution I or 1.1-1.7 wherein the salt solution        comprises at least a 1:2 molar ratio of Formula II to the        protonated amine, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to        1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.9 Salt Solution 1.8 wherein the salt solution comprises at        least a 1:2 molar ratio of Formula II to the protonated mono-        and/or poly-hydroxyalkylamine, e.g., (HO)_(n)R⁸NH₃ ^(|),        [(HO)_(n)R⁸]₂NH₂ ^(|), [(HO)_(n)R⁸]₃NH^(|), wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,

-   -    e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.10 Salt Solution 1.8-1.10 wherein the salt solution comprises        at least a 1:2 molar ratio of Formula II to (HO)_(n)R⁸NH₃,        [(HO)_(n)R⁸]₂NH₂ ⁺, [(HO)_(n)R⁸]₃NH⁺, wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₈-s-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,

-   -    e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.11 Salt Solution 1.8-1.10 wherein the salt solution comprises        at least a 1:2 molar ratio of Formula II to

-   -    e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.12 Salt Solution 1.8-1.10 wherein the salt solution comprises        at least a 1:2 molar ratio of Formula II to

-   -    e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.13 Salt Solution I or 1.1-1.6 wherein the salt solution        comprises at least a 1:2 molar ratio of Formula III to the        protonated amine, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to        1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.14 Salt Solution 1.13 wherein the salt solution comprises at        least a 1:2 molar ratio of Formula III to the protonated mono-        and/or poly-hydroxyalkylamine, e.g., (HO)_(n)R⁸NH₃ ⁺,        [(HO)_(n)R⁸]₂NH₂ ⁺, [(HO)_(n)R⁸]₃NH⁺, wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,

-   -    e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.15 Salt Solution 1.13-1.14 wherein the salt solution comprises        at least a 1:2 molar ratio of Formula III to (HO)_(n)R⁸NH₃ ⁺,        [(HO)_(n)R⁸]₂NH₂ ⁺, [(HO)_(n)R⁸]₃NH⁺, wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,

-   -    e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.16 Salt Solution 1.13-1.15 wherein the salt solution comprises        at least a 1:2 molar ratio of Formula III to

-   -    e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.17 Salt Solution 1.14-1.16 wherein the salt solution comprises        at least a 1:2 molar ratio of Formula III to

-   -    e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.18 Salt Solution 1.14-1.16 wherein the salt solution comprises        at least a 1:2 molar ratio of Formula III to

-   -    e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.19 Salt Solution I or 1.1-1.18 wherein the solvent is a        sterile solution, e.g., sterile water for injection, a sterile        solution comprising dextrose (e.g., dextrose injection 5%), a        sterile solution comprising sodium chloride (e.g., 0.9% sodium        chloride injection), a sterile solution comprising benzyl        alcohol (e.g., bacteriostatic water for injection with benzyl        alcohol or bacteriostatic sodium chloride for injection with        benzyl alcohol), or Lactated Ringer's.    -   1.20 Salt Solution I or 1.1-1.19 wherein the salt solution        comprises 0.5 to 500 mL solvent, e.g., an aqueous solution,        e.g., from about 1 or 2 mL to 500 mL, e.g., from about 1 or 2 mL        to 5, 10, 25, 30, 35, 50, 75, 100, 150, 200, 300 or 500 mL,        e.g., from about 1 or 2 mL to 5, 10, 25, 50, 75, 100, or 200 mL,        e.g., from about 3.5 or 5 to 10, 25, 50, or 100 mL, e.g., about        3.5 or 35 mL.    -   1.21 Salt Solution I or 1.1-1.20 wherein the salt solution        comprises 0.5 to 500 mL sterile solution, e.g., sterile water        for injection, a sterile solution comprising dextrose (e.g.,        dextrose injection 5%), a sterile solution comprising sodium        chloride (e.g., 0.9% sodium chloride injection), a sterile        solution comprising benzyl alcohol (e.g., bacteriostatic water        for injection with benzyl alcohol or bacteriostatic sodium        chloride for injection with benzyl alcohol), or Lactated        Ringer's, e.g., from about 1 or 2 mL to 500 mL, e.g., from about        1 or 2 mL to 5, 10, 25, 30, 35, 50, 75, 100, 150, 200, 300 or        500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 50, 75, 100, or        200 mL, e.g., from about 3.5 or 5 to 10, 25, 50, or 100 mL,        e.g., about 3.5 or 35 mL.    -   1.22 Salt Solution I or 1.1-1.21 wherein the salt solution        comprises sterile water for injection or a sterile solution        comprising sodium chloride (e.g., 0.9% sodium chloride        injection).    -   1.23 Salt Solution I or 1.1-1.22 wherein the salt solution        comprises sterile water for injection.    -   1.24 Salt Solution 1.23 wherein the salt solution comprises 0.5        to 500 mL sterile water for injection, e.g., from about 1 or 2        mL to 500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 30, 35,        50, 75, 100, 150, 200, 300 or 500 mL, e.g., from about 1 or 2 mL        to 5, 10, 25, 50, 75, 100, or 200 mL, e.g., from about 3.5 or 5        to 10, 25, 50, or 100 mL, e.g., about 3.5 or 35 mL.    -   1.25 Salt Solution I or 1.1-1.24 wherein the salt solution        comprises a sterile solution comprising sodium chloride (e.g.,        0.9% sodium chloride injection).    -   1.26 Salt Solution 1.25 wherein the salt solution comprises 0.5        to 500 mL of a sterile solution comprising sodium chloride        (e.g., 0.9% sodium chloride injection), e.g., from about 1 or 2        mL to 500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 30, 35,        50, 75, 100, 150, 200, 300 or 500 mL, e.g., from about 1 or 2 mL        to 5, 10, 25, 50, 75, 100, or 200 mL, e.g., from about 3.5 or 5        to 10, 25, 50, or 100 mL, e.g., about 3.5 or 35 mL.    -   1.27 Salt Solution I or 1.1-1.26 wherein the concentration of        Formula II or Formula III, e.g., the concentration of Formula        II, e.g, the concentration of Formula III is 0.01 or 0.02 or        0.05 or 0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or        0.1 or 0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125,        150, 175, 200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10,        15, 20, 25, 40, 50 or 60 mM, e.g., from about 5, 10, 15, 20, 25,        or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about        2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM.    -   1.28 Salt Solution I or 1.1-1.27 wherein the salt solution        comprises one or more bulking agents, e.g., one or more of        maltose, mannose, ribose, cyclodextrin, mannitol, lactose,        sucrose, trehalose, sorbitol, glucose, raffinose, arginine,        glycine, histidine, dextran (e.g., dextran 40),        polyvinylpyrrolidone, polyethylene glycol, and polypropylene        glycol, e.g., one or more of mannitol, glucose, sucrose,        lactose, trehalose, and dextran (e.g., dextran 40).    -   1.29 Salt Solution I or 1.1-1.28 wherein the salt solution        comprises 5 or 10 or 50 mg to 2 or 5 g of one or more bulking        agents, e.g., from about 50 or 100 mg to 200, 300, 500, or 800        mg, or 1, 1.5, 2, 3, 4, or 5 g of one or more bulking agents.    -   1.30 Salt Solution I or 1.1-1.29 wherein the salt solution        comprises dextran (e.g., dextran 40).    -   1.31 Salt Solution 1.30 wherein the salt solution comprises 5 or        10 or 50 mg to 2 or 5 g dextran (e.g., dextran 40), e.g., from        about 50 or 100 mg to 200, 300, 500, or 800 mg, or 1, 1.5, 2, 3,        4, or 5 g dextran (e.g., dextran 40).    -   1.32 Salt Solution I or 1.1-1.31 wherein the salt solution        comprises one or more solubilizing agents, e.g., ethylenediamine        tetraacetic acid (EDTA) or a salt thereof (e.g., calcium        disodium EDTA, disodium EDTA, sodium EDTA), alpha cyclodextrin,        hydroxypropyl-β-cyclodextrin, polysorbate 80, tert-butanol,        isopropanol, dichloromethane, ethanol, acetone, and glycerol;        one or more collapse temperature modifiers which may shift the        overall collapse temperature higher, e.g., one or more of        dextran, Ficoll®, gelatin, and hydroxyethyl starch; one or more        tonicity modifiers, e.g., one or more of sodium chloride,        potassium chloride, sucrose, mannitol, and glucose; and one or        more antimicrobial agents, e.g., one or more of benzyl alcohol,        phenol, 2-phenoxyethanol, m-cresol, chlorobutanol, parabens        (e.g., methyl paraben, ethyl paraben, propyl paraben),        benzalkonium chloride, benzethonium chloride, myristyl        gamma-picolinium salt (e.g., myristyl gamma-picolinium        chloride), and organomercury compounds and salts (e.g., phenyl        mercuric acetate, phenyl mercuric borate, phenyl mercuric        nitrate, and thimerosal).    -   1.33 Salt Solution I or 1.1-1.32 wherein the pH of the salt        solution is between pH 7 and pH 10.5, e.g., between pH 7 and pH        9.5, e.g., between pH 7 and pH 8, e.g., between 7.5 and 8.5,        e.g., 7.5, e.g., 8.5, e.g., 8.2.    -   1.34 Salt Solution I or 1.1-1.33 wherein the salt solution is        filtered to remove particles and microbes, e.g., filtered prior        to injection.    -   1.35 Salt Solution I or 1.1-1.34 wherein the salt solution is        for injection, e.g., subcutaneously, intramuscularly,        intravenously, or intrathecally, e.g., intramuscularly or        intravenously, e.g., a bolus injected subcutaneously,        intramuscularly, intravenously, or intrathecally.    -   1.36 Salt Solution 1.35 wherein the salt solution is for        injection intravenously, e.g., IV bolus and/or IV infusion,        e.g., IV bolus followed by IV infusion, e.g., a loading bolus        (e.g., 10 or 20 to 30, 50, 70, 75, 100, 140, 150, 200, 300 or        400 mg per day administered by a loading bolus dose, e.g., about        50 to 200 or 250 mg per day administered by a loading bolus        dose, e.g., about 70 to 140 mg per day administered by a loading        bolus dose, e.g., a concentration of the dissolved salt        administered by a loading bolus dose of 1 to 4, 5, 8, 10, 15,        20, 30, or 50 mM per day, e.g., a concentration of the dissolved        salt administered by a loading bolus dose of about 2 to 5, 10,        15, or 20 mM per day, e.g., a concentration of the dissolved        salt administered by a loading bolus dose of about 4 to 8 or 9        mM per day) and then an IV infusion over 24 hours for 3 days        (e.g., at a rate of 1, 2, 3, 5, 6, 7, 8, 10, 15, 20, 25, 30, or        50 mg/hr for 24 hours, e.g., at a rate of 3, 6, or 15 mg/hr).    -   1.37 Salt Solution 1.35 wherein the salt solution is for        injection intramuscularly, e.g., IM bolus and/or IM infusion,        e.g., IM bolus followed by IM infusion.    -   1.38 Salt Solution 1.36 or 1.37 wherein the infusion, e.g., IV        or IM, is administered over about 10 or 30 minutes to 72 hours,        e.g., about 30 minutes to 24 hours, e.g, about 30 minutes to 12        hours, e.g., about 30 minutes to 8 hours, e.g., about 30 minutes        to 6 hours, e.g., about 30 minutes to 4 hours, e.g., about 30        minutes to 2 hours, e.g., about 30 minutes to 1 hour, e.g.,        about 72 hours.    -   1.39 Salt Solution I or 1.1-111.39111.38 wherein the salt        solution comprises one or more additional therapeutic agents,        e.g., one or more additional therapeutic agents for cerebral        edema, stroke, traumatic brain injury, glioma (e.g.,        glioblastoma), meningitis, acute mountain sickness, infection,        metabolic disorder, hypoxia, water intoxication, hepatic        failure, hepatic encephalopathy, diabetic ketoacidosis, abscess,        eclampsia, Creutzfeldt-Jakob disease, lupus cerebritis, optic        nerve edema, hyponatremia, fluid retention, ovarian        hyperstimulation syndrome, epilepsy, retinal ischemia or other        diseases of the eye associated with abnormalities in intraocular        pressure and/or tissue hydration, myocardial ischemia,        myocardial ischemia/reperfusion injury, myocardial infarction,        myocardial hypoxia, congestive heart failure, sepsis,        neuromyelitis optica, or migraines.    -   1.40 Salt Solution I or 1.1-1.39 wherein the salt solution        comprises one or more additional therapeutic agents, e.g., one        or more additional therapeutic agents for pulmonary edema,        fibromyalgia, or multiple sclerosis.    -   1.41 Salt Solution I or 1.1-1.40 wherein the salt solution is        stable for at least one week, at room temperature, e.g., for at        least 1, 2, 4, 6, 8, or 12 months, e.g., the composition has        <20%        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        <15%        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        <10%        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        <5%        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        <2%        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        1%        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        or <1%        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide.    -   1.42 Salt Solution I or 1.1-1.41 wherein the salt solution        comprises less than 10%, 15%, or 20% of        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        e.g., less than 5, 4, 3, or 2% of        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide        for at least one week, e.g., for at least 1, 2, 4, 6, 8, or 12        months.    -   1.43 Salt Solution I or 1.1-1.42 wherein the salt solution is        administered concurrently or sequentially, in either order, with        one or more additional therapeutic agents, e.g., one or more        additional therapeutic agents for cerebral edema, stroke,        traumatic brain injury, glioma (e.g., glioblastoma), meningitis,        acute mountain sickness, infection, metabolic disorder, hypoxia,        water intoxication, hepatic failure, hepatic encephalopathy,        diabetic ketoacidosis, abscess, eclampsia, Creutzfeldt-Jakob        disease, lupus cerebritis, optic nerve edema, hyponatremia,        fluid retention, ovarian hyperstimulation syndrome, epilepsy,        retinal ischemia or other diseases of the eye associated with        abnormalities in intraocular pressure and/or tissue hydration,        myocardial ischemia, myocardial ischemia/reperfusion injury,        myocardial infarction, myocardial hypoxia, congestive heart        failure, sepsis, neuromyelitis optica, or migraines.    -   1.44 Salt Solution I or 1.1-1.43 wherein the salt solution is        administered concurrently or sequentially, in either order, with        one or more additional therapeutic agents, e.g., one or more        additional therapeutic agents for pulmonary edema, fibromyalgia,        or multiple sclerosis.    -   1.45 Salt Solution I or 1.1-1.44 wherein the salt solution is        for use in any of the methods described herein, e.g., for use in        Method A, e.g., Method A.1-A.58, for use in Method B, e.g.,        Method B.1-B.41, e.g., for use in Method C, e.g., C.1-C.8, e.g.,        for use in Method D, e.g., D.1-D.19, e.g., for use in Method E,        e.g., E.1-E.59, e.g., for use in Method F, e.g., F.1-F.5, e.g.,        for use in Method G, e.g., G.1-G.58, for use in Method H, e.g.,        H.1-H.9, vida infra.

In yet another embodiment, provided is a method (Method II) for making asalt solution, e.g., Salt Solution I, e.g., Salt Solution 1.1-1.46,comprising admixing a compound of Formula I

and an amine and/or a salt thereof (e.g., morpholine, piperazine,benethamine, benzathine, trimethylglycine, hydrabamine,4-(2-hydroxyethyl)morpholine, 1-(2 hydroxethyl)-pyrrolidine, an aminoacid (e.g., arginine and/or lysine), a mono- and/orpoly-hydroxyalkylamine, and/or a salt thereof, e.g., (HO)_(n)R⁸NH₂,[(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N and/or a salt thereof wherein each R⁸ isindependently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g.,—CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene,e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is—CH₃ and another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane (also knownas tris base) and/or a salt thereof (e.g.,tris(hydroxymethyl)aminomethane acetate (also known as tris acetate),meglumine, dimethylethanolamine, diethylamine, diethylethanolamine,and/or diethanolamine), e.g., any of the preceding wherein a conjugateacid of the amine and/or salt thereof has a pKa between 6, 7, 8, 9, or10 and 11, e.g., between about 6, 7, 8, or 9 and 10, e.g., between about7 and 9, e.g., between about 8 and 9, in a solvent, e.g., an aqueoussolution.

Further provided is Method II as follows:

-   -   2.1 Method II comprising admixing the compound of Formula I with        a mono- and/or poly-hydroxyalkylamine and/or a salt thereof,        e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, and/or [(HO)_(n)R⁸]₃N        and/or a salt thereof, wherein each R⁸ is independently        C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃,        e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene,        e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., C(CH₂)₃—, e.g., one        R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and each n is        independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,

-   -    and/or a salt thereof, e.g., any of the preceding wherein a        conjugate acid of the amine and/or salt thereof has a pKa        between 6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7, 8,        or 9 and 10, e.g., between about 7 and 9, e.g., between about 8        and 9.    -   2.2 Method II or 2.1 comprising admixing the compound of Formula        I with (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, and/or [(HO)_(n)R⁸]₃N        and/or salt thereof (e.g., acetate, e.g.,        tris(hydroxymethyl)aminomethane acetate), wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.

-   -    and/or a salt thereof.    -   2.3 Method II, 2.1, or 2.2 comprising admixing the compound of        Formula I with

-   -    and/or a salt thereof (e.g., tris(hydroxymethyl)aminomethane        acetate).    -   2.4 Method II or 2.1-2.3 comprising admixing the compound of        Formula I with

-   -    and/or a salt thereof.    -   2.5 Method II or 2.1-2.4 comprising admixing the compound of        Formula I with

-   -    and/or a salt thereof.    -   2.6 Method II or 2.1-2.5 wherein Formula I and the amine and/or        salt thereof are admixed in at least a 1:1 molar ratio.    -   2.7 Method II or 2.1-2.6 wherein Formula I and the amine and/or        salt thereof are admixed in at least a 1:2 molar ratio, e.g., at        least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to 1:10,        1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5, 1:6,        1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   2.8 Method 11 or 2.1-2.7 wherein Formula I and the mono- and/or        poly-hydroxyalkylamine and/or salt thereof, e.g., (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, and/or [(HO)_(n)R⁸]₃N and/or salt thereof        and/or salt thereof (e.g., acetate, e.g.,        tris(hydroxymethyl)aminomethane acetate), wherein each R⁸ is        independently C₁₋₈-alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,

-   -    and/or a salt thereof, e.g., any of the preceding wherein a        conjugate acid of the amine and/or salt thereof has a pKa        between 6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7, 8,        or 9 and 10, e.g., between about 7 and 9, e.g., between about 8        and 9, are admixed in at least a 1:2 molar ratio, e.g., at least        about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to 1:10, 1:15,        1:20, or 1:30, e.g., at least about 1:2.5 to 1:5, 1:6, 1:7, 1:8,        1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5,        e.g., at least about 1:5, e.g. at least about 1:10.    -   2.9 Method II or 2.1-2.8 wherein Formula I and (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, and/or [(HO)_(n)R⁸]₃N and/or salt thereof        (e.g., acetate, e.g., tris(hydroxymethyl)aminomethane acetate),        wherein each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl,        e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g.,

-   -    and/or a salt thereof are admixed in at least a 1:2 molar        ratio, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7,        1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to        1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at        least about 1:2.5, e.g., at least about 1:5, e.g. at least about        1:10.    -   2.10 Method 11 or 2.1-2.9 wherein Formula I and

-   -    and/or a salt thereof are admixed in at least a 1:2 molar        ratio, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7,        1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to        1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at        least about 1:2.5, e.g., at least about 1:5, e.g. at least about        1:10.    -   2.11 Method II or 2.1-2.10 wherein Formula I and

-   -    and/or a salt thereof are admixed in at least a 1:2 molar        ratio, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7,        1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to        1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at        least about 1:2.5, e.g., at least about 1:5, e.g. at least about        1:10.    -   2.12 Method II or 2.1-2.11 wherein Formula I and

-   -    and/or a salt thereof are admixed in at least a 1:2 molar        ratio, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7,        1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to        1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at        least about 1:2.5, e.g., at least about 1:5, e.g. at least about        1:10.    -   2.13 Method II or 2.1-2.12 wherein the solvent is a sterile        solution, e.g., sterile water for injection, a sterile solution        comprising dextrose (e.g., dextrose injection 5%), a sterile        solution comprising sodium chloride (e.g., 0.9% sodium chloride        injection), a sterile solution comprising benzyl alcohol (e.g.,        bacteriostatic water for injection with benzyl alcohol or        bacteriostatic sodium chloride for injection with benzyl        alcohol), or Lactated Ringer's.    -   2.14 Method II or 2.1-2.13 wherein there is 0.5 to 500 mL of        solvent, e.g., an aqueous solution, e.g., from about 1 or 2 mL        to 500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 30, 35, 50,        75, 100, 150, 200, 300 or 500 mL, e.g., from about 1 or 2 mL to        5, 10, 25, 50, 75, 100, or 200 mL, e.g., from about 3.5 or 5 to        10, 25, 50, or 100 mL, e.g., about 3.5 or 35 mL.    -   2.15 Method 11 or 2.1-2.14 wherein there is 0.5 to 500 mL of        sterile solution, e.g., sterile water for injection, a sterile        solution comprising dextrose (e.g., dextrose injection 5%), a        sterile solution comprising sodium chloride (e.g., 0.9% sodium        chloride injection), a sterile solution comprising benzyl        alcohol (e.g., bacteriostatic water for injection with benzyl        alcohol or bacteriostatic sodium chloride for injection with        benzyl alcohol), or Lactated Ringer's, e.g., from about 1 or 2        mL to 500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 30, 35,        50, 75, 100, 150, 200, 300 or 500 mL, e.g., from about 1 or 2 mL        to 5, 10, 25, 50, 75, 100, or 200 mL, e.g., from about 3.5 or 5        to 10, 25, 50, or 100 mL, e.g., about 3.5 or 35 mL.    -   2.16 Method II or 2.1-2.15 wherein the solvent comprises sterile        water for injection or a sterile solution comprising sodium        chloride (e.g., 0.9% sodium chloride injection).    -   2.17 Method II or 2.1-2.16 wherein the solvent comprises sterile        water for injection.    -   2.18 Method II or 2.1-2.17 wherein the solvent comprises 0.5 to        500 mL sterile water for injection, e.g., from about 1 or 2 mL        to 500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 30, 35, 50,        75, 100, 150, 200, 300 or 500 mL, e.g., from about 1 or 2 mL to        5, 10, 25, 50, 75, 100, or 200 mL, e.g., from about 3.5 or 5 to        10, 25, 50, or 100 mL, e.g., about 3.5 or 35 mL.    -   2.19 Method II or 2.1-2.18 wherein the solvent comprises a        sterile solution comprising sodium chloride (e.g., 0.9% sodium        chloride injection).    -   2.20 Method 2.19 wherein the solvent comprises 0.5 to 500 mL of        a sterile solution comprising sodium chloride (e.g., 0.9% sodium        chloride injection), e.g., from about 1 or 2 mL to 500 mL, e.g.,        from about 1 or 2 mL to 5, 10, 25, 30, 35, 50, 75, 100, 150,        200, 300 or 500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 50,        75, 100, or 200 mL, e.g., from about 3.5 or 5 to 10, 25, 50, or        100 mL, e.g., about 3.5 or 35 mL.    -   2.21 Method II or 2.1-2.20 wherein the concentration of the        compound of Formula I is 0.01 or 0.02 or 0.05 or 0.1 or 0.5 or 1        or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to 1, 2, 5,        10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175, 200, 250, or        1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25, 40, 50 or 60        mM, e.g., from about 5, 10, 15, 20, 25, or 50 to 100, 200, 250,        300, 400, 500, or 1000 mM, e.g., about 2, 20, or 200 mM, e.g.,        about 5, 10, 50, 500, 500, or 1000 mM.    -   2.22 Method II or 2.1-2.21 wherein the solvent, e.g., an aqueous        solution, comprises one or more bulking agents, e.g., one or        more of maltose, mannose, ribose, cyclodextrin, mannitol,        lactose, sucrose, trehalose, sorbitol, glucose, raffinose,        arginine, glycine, histidine, dextran (e.g., dextran 40),        polyvinylpyrrolidone, polyethylene glycol, and polypropylene        glycol, e.g., one or more of mannitol, glucose, sucrose,        lactose, trehalose, and dextran (e.g., dextran 40).    -   2.23 Method 11 or 2.1-2.22 wherein the solvent, e.g., an aqueous        solution, comprises 5 or 10 or 50 mg to 2 or 5 g of one or more        bulking agents, e.g., from about 50 or 100 mg to 200, 300, 500,        or 800 mg, or 1, 1.5, 2, 3, 4, or 5 g of one or more bulking        agents.    -   2.24 Method II or 2.1-2.23 wherein the solvent, e.g., an aqueous        solution, comprises dextran (e.g., dextran 40).    -   2.25 Method II or 2.1-2.24 wherein the solvent, e.g., an aqueous        solution, comprises 5 or 10 or 50 mg to 2 or 5 g dextran (e.g.,        dextran 40), e.g., from about 50 or 100 mg to 200, 300, 500, or        800 mg, or 1, 1.5, 2, 3, 4, or 5 g dextran (e.g., dextran 40).    -   2.26 Method II or 2.1-2.25 wherein the solvent, e.g., an aqueous        solution, comprises one or more solubilizing agents, e.g.,        ethylenediamine tetraacetic acid (EDTA) or a salt thereof (e.g.,        calcium disodium EDTA, disodium EDTA, sodium EDTA), alpha        cyclodextrin, hydroxypropyl-β-cyclodextrin, polysorbate 80,        tert-butanol, isopropanol, dichloromethane, ethanol, acetone,        and glycerol; one or more collapse temperature modifiers which        may shift the overall collapse temperature higher, e.g., one or        more of dextran, Ficoll®, gelatin, and hydroxyethyl starch; one        or more tonicity modifiers, e.g., one or more of sodium        chloride, potassium chloride, sucrose, mannitol, and glucose;        and one or more antimicrobial agents, e.g., one or more of        benzyl alcohol, phenol, 2-phenoxyethanol, m-cresol,        chlorobutanol, parabens (e.g., methyl paraben, ethyl paraben,        propyl paraben), benzalkonium chloride, benzethonium chloride,        myristyl gamma-picolinium salt (e.g., myristyl gamma-picolinium        chloride), and organomercury compounds and salts (e.g., phenyl        mercuric acetate, phenyl mercuric borate, phenyl mercuric        nitrate, and thimerosal).    -   2.27 Method II or 2.1-2.26 wherein the pH of the salt solution        is between pH 7 and pH 10.5, e.g., between pH 7 and pH 9.5,        e.g., between pH 7 and pH 8, e.g., between 7.5 and 8.5, e.g.,        7.5, e.g., 8.5, e.g., 8.2.    -   2.28 Method II or 2.1-2.27 further comprising filter the salt        solution to remove particles and microbes, e.g., filtered prior        to injection.    -   2.29 Method II or 2.1-2.28 further comprising admixing the salt        Solution with one or more additional therapeutic agents, e.g.,        one or more additional therapeutic agents for cerebral edema,        stroke, traumatic brain injury, glioma (e.g., glioblastoma),        meningitis, acute mountain sickness, infection, metabolic        disorder, hypoxia, water intoxication, hepatic failure, hepatic        encephalopathy, diabetic ketoacidosis, abscess, eclampsia,        Creutzfeldt-Jakob disease, lupus cerebritis, optic nerve edema,        hyponatremia, fluid retention, ovarian hyperstimulation        syndrome, epilepsy, retinal ischemia or other diseases of the        eye associated with abnormalities in intraocular pressure and/or        tissue hydration, myocardial ischemia, myocardial        ischemia/reperfusion injury, myocardial infarction, myocardial        hypoxia, congestive heart failure, sepsis, neuromyelitis optica,        or migraines.    -   2.30 Method II or 2.1-2.29 further comprising admixing the salt        solution with one or more additional therapeutic agents, e.g.,        one or more additional therapeutic agents for pulmonary edema,        fibromyalgia, or multiple sclerosis.

In yet another embodiment, provided is a kit (Kit I) comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate.

Further provided is Kit I as follows:

-   -   1.1 Kit I wherein the kit comprises 0.1 or 0.25 mg to 2.0 g        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate, e.g., from about 0.1 or 0.25 mg to 75 or        600 mg, e.g., from about 0.1 or 0.25 or 1 or 2 mg to 50, 75,        100, 125, 150, 200, 300, 350, 400, 500, or 600 mg, or 1 g, 1.5        g, or 2.0 g, e.g., from about 5 to 50, 75, 100, 125, 150, 200,        300, 350, 400, 500, or 600 mg, or 1 g, 1.5 g, or 2, e.g., from        about 5 to 500 mg, e.g., from about 5 to 300 or 350 mg, e.g.,        from about 5 to 200 mg, e.g., from about 25 to 500 mg, e.g.,        from about 25 to 300 or 350 mg, e.g., from about 25 to 200 mg,        e.g., from about 15, 20, 30, 35, 50 or 100 to 150, 200, 300,        350, 400, 450, 500, 550, or 600 mg, e.g., from about 0.5 or 1 mg        to 50 mg, e.g., from about 0.5 or 1 mg to 20 mg, e.g., from        about 0.5 or 1 mg to 10 mg, e.g., from about 1 or 2 or 5 mg to        10 or 20 mg, eg., from about 1 or 2 or 3 or 4 or 5 mg, e.g.,        about 35 mg, e.g. about 35 mg, or wherein the kit comprises        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate in an amount sufficient to provide 0.1 or        0.25 mg to 2.0 g of        N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,        e.g., from about 0.1 or 0.25 mg to 75 or 600 mg, e.g., from        about 0.1 or 0.25 or 1 or 2 mg to 50, 75, 100, 125, 150, 200,        300, 350, 400, 500, or 600 mg, or 1 g, 1.5 g, or 2.0 g, e.g.,        from about 5 to 50, 75, 100, 125, 150, 200, 300, 350, 400, 500,        or 600 mg, or 1 g, 1.5 g, or 2 g, e.g., from about 5 to 500 mg,        e.g., from about 5 to 300 or 350 mg, e.g., from about 5 to 200        mg, e.g., from about 25 to 500 mg, e.g., from about 25 to 300 or        350 mg, e.g., from about 25 to 200 mg, e.g., from about 15, 20,        30, 35, 50 or 100 to 150, 200, 300, 350, 400, 450, 500, 550, or        600 mg, e.g., from about 0.5 or 1 mg to 50 mg, e.g., from about        0.5 or 1 mg to 20 mg, e.g., from about 0.5 or 1 mg to 10 mg,        e.g., from about 1 or 2 or 5 mg to 10 or 20 mg, eg., from about        1 or 2 or 3 or 4 or 5 mg, e.g., about 35 mg, e.g. about 35 mg.    -   1.2 Kit I or 1.1 wherein the kit comprises one or more        pharmaceutically acceptable excipients.    -   1.3 Kit 1.2 wherein the one or more pharmaceutically acceptable        excipients comprise one or more of bases, bulking agents,        solubilizing agents, collapse temperature modifiers, tonicity        modifiers, and antimicrobial agents.    -   1.4 Kit 1.2 or 1.3 wherein the one or more pharmaceutically        acceptable excipients comprise one or more bases, e.g., a base        wherein upon dissolution of the composition in a solvent, e.g.,        an aqueous solution, the solution has a pH between 7, 7.5, or 8        and 10.5, e.g., between about 7, 7.5, or 8 and 9.5, e.g.,        between about 7 or 7.5 and 8, e.g., between about 7.5 and 8.5,        e.g., about 7.5, e.g., about 8.5, e.g., between about 8 and 8.5,        e.g., about 8.2, e.g., a base wherein a conjugate acid of the        base has a pKa between 6, 7, 8, 9, or 10 and 11, e.g., between        about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9, e.g.,        between about 8 and 9, e.g., wherein the one or more bases are        one or more of:        -   a) a C₁₋₈-alkyl mono-, di-, or tri-carboxylic acid salt,            e.g., a citrate salt, e.g, a metal citrate salt (e.g., an            alkali and/or alkaline citrate salt, e.g., an alkali citrate            salt, e.g., sodium citrate and/or potassium citrate), e.g.,            a tartrate salt (e.g., a metal tartrate salt, an alkali            tartrate, e.g., sodium tartrate), e.g., a succinate salt            (e.g., a metal succinate salt, e.g., an alkali succinate,            e.g., disodium succinate), and/or e.g., a lactate salt            (e.g., a metal lactate salt, e.g., an alkali lactate, e.g.,            sodium lactate),        -   b) a phosphate salt, e.g., a metal phosphate salt (e.g., an            alkali and/or alkaline phosphate salt, e.g., an alkali            phosphate salt, e.g., sodium phosphate (e.g., NaH₂PO₄ and/or            Na₂HPO₄) and/or potassium phosphate (e.g., KH₂PO₄ and/or            K₂HPO₄)),        -   c) an amine and/or a salt thereof (e.g., morpholine,            piperazine, benethamine, benzathine, trimethylglycine,            hydrabamine, 4-(2-hydroxyethyl)morpholine,            1-2-hydroxyethyl)-pyrrolidine, an amino acid (e.g., arginine            and/or lysine), a mono- and/or poly-hydroxyalkylamine,            and/or a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,            [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each R⁸ is            independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,            e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene            (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—,            e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is            —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,            5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known            as tris base) and/or a salt thereof (e.g.,            tris(hydroxymethyl)aminomethane acetate (also known as tris            acetate), meglumine, dimethylethanolamine, diethylamine,            diethylethanolamine, and/or diethanolamine), e.g., any of            the preceding wherein a conjugate acid of the amine and/or            salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,            e.g., between about 6, 7, 8, or 9 and 10, e.g., between            about 7 and 9, e.g., between about 8 and 9 between 6 and 11,            e.g., between 6.5 and 10, e.g., between 7 and 9,        -   d) a metal chloride salt (e.g., zinc chloride),        -   e) an acetate salt, e.g., a metal acetate salt (e.g., an            alkali and/or alkaline acetate salt, e.g., an alkali acetate            salt, e.g., sodium acetate and/or potassium acetate),        -   f) a hydroxide and/or alkoxide salt, e.g., a metal hydroxide            and/or alkoxide salt (e.g., a quarternary ammonium            hydroxide, e.g., ammonium hydroxide and/or choline            hydroxide, lithium hydroxide, aluminum hydroxide, e.g., an            alkali and/or alkaline hydroxide salt, e.g., sodium            hydroxide, potassium hydroxide, calcium hydroxide, magnesium            hydroxide, and/or magnesium ethoxide, e.g., sodium            hydroxide),        -   g) a carbonate and/or bicarbonate salt, e.g., a metal            carbonate and/or metal bicarbonate salt (e.g., an alkali            and/or alkaline carbonate salt, e.g., an alkali and/or            alkaline bicarbonate salt, e.g., sodium bicarbonate),        -   h) a metal borate salt (e.g., an alkali borate salt, e.g.,            sodium borate),    -    e.g., one or more of sodium citrate, Na₂HPO₄,        tris(hydroxymethyl)aminomethane, and a        tris(hydroxymethyl)aminomethane salt (e.g., tris acetate), e.g.,        one or more of sodium citrate, Na₂HPO₄, and        tris(hydroxymethyl)aminomethane, e.g., one or more of sodium        citrate and Na₂HPO₄, e.g., Na₂HPO₄, e.g.,        tris(hydroxymethyl)aminomethane.    -   1.5 Kit 1.2-1.4 wherein the one or more pharmaceutically        acceptable excipients comprise one or more bases, e.g., a base        wherein upon dissolution of the composition in a solvent, e.g.,        an aqueous solution, the solution has a pH between 7, 7.5, or 8        and 10.5, e.g., between about 7, 7.5, or 8 and 9.5, e.g.,        between about 7 or 7.5 and 8, e.g., between about 7.5 and 8.5,        e.g., about 7.5, e.g., about 8.5, e.g., between about 8 and 8.5,        e.g., about 8.2, e.g., a base wherein a conjugate acid of the        base has a pKa between 6, 7, 8, 9, or 10 and 11, e.g., between        about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9, e.g.,        between about 8 and 9, e.g., wherein the one or more bases are        one or more of:        -   a) a metal citrate salt (e.g., an alkali and/or alkaline            citrate salt, e.g., an alkali citrate salt, e.g., sodium            citrate and/or potassium citrate),        -   b) a metal phosphate salt (e.g., an alkali and/or alkaline            phosphate salt, e.g., an alkali phosphate salt, e.g., sodium            phosphate (e.g., NaH₂PO₄ and/or Na₂HPO₄) and/or potassium            phosphate (e.g., KH₂PO₄ and/or K₂HPO₄)),        -   c) an amine and/or a salt thereof (e.g., morpholine, an            amino acid (e.g., arginine), a mono- and/or            poly-hydroxyalkylamine, and/or a salt thereof, e.g.,            (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a            salt thereof wherein each R⁸ is independently C₁₋₈alkyl            (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g.,            —CH₃) and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene,            e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g.,            one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and each n is            independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,            tris(hydroxymethyl)aminomethane (also known as tris base)            and/or a salt thereof (e.g., tris(hydroxymethyl)aminomethane            acetate (also known as tris acetate), meglumine, and/or            diethanolamine), e.g., any of the preceding wherein a            conjugate acid of the amine and/or salt thereof has a pKa            between 6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7,            8, or 9 and 10, e.g., between about 7 and 9, e.g., between            about 8 and 9,        -   d) a metal acetate salt (e.g., an alkali and/or alkaline            acetate salt, e.g., an alkali acetate salt, e.g., sodium            acetate and/or potassium acetate),        -   e) a metal hydroxide salt (e.g., an alkali and/or alkaline            hydroxide salt, e.g., sodium hydroxide, potassium hydroxide,            calcium hydroxide, and/or magnesium hydroxide, e.g., sodium            hydroxide),        -   f) a metal carbonate and/or bicarbonate salt (e.g., an            alkali and/or alkaline carbonate salt, e.g., an alkali            and/or alkaline bicarbonate salt, e.g., sodium bicarbonate),            and/or        -   g) a metal borate salt (e.g., an alkali borate salt, e.g.,            sodium borate),    -    e.g., one or more of sodium citrate, Na₂HPO₄,        tris(hydroxymethyl)aminomethane, and a        tris(hydroxymethyl)aminomethane salt (e.g., tris acetate), e.g.,        one or more of sodium citrate, Na₂HPO₄, and        tris(hydroxymethyl)aminomethane, e.g., one or more of sodium        citrate and Na₂HPO₄, e.g., Na₂HPO₄, e.g.,        tris(hydroxymethyl)aminomethane.    -   1.6 Kit 1.3-1.5 wherein the kit comprises 1 or 5 mg to 200 or        500 mg of one or more bases, e.g., from about 1 or 5 or 10 mg to        15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300, 350, 400,        450, 500, 1000, or 1500 mg, e.g., from about 15, 20, 30, 50, or        100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.7 Kit 1.3-1.5 wherein the concentration of each of the one or        more bases is 0.01 or 0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from        about 0.01 or 0.1 or 0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60,        75, 100, 125, 150, 175, 200, 250, or 1000 mM, e.g. from about 1        to 2, 5, 10, 15, 20, 25, 40, 50 or 60 mM, e.g., from about 5 to        50 mM, e.g., from about 5, 10, 15, 20, 25, or 50 to 100, 200,        250, 300, 400, 500, or 1000 mM, e.g., about 2, 20, or 200 mM,        e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g., from about 5,        10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500, or 1000        mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50, 500,        500, or 1000 mM, e.g., wherein the concentration of each of the        one or more bases is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents        of Formula II, e.g., about 2.5 or 5 to 10, e.g. about 2.5, e.g.,        about 5, e.g., wherein the concentration of each of the one or        more bases is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of        Formula III, e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.8 Kit 1.3-1.6 wherein the one or more bases comprise one or        more of a metal citrate salt (e.g., sodium citrate) and a metal        phosphate salt (e.g., sodium phosphate, e.g., Na₂HPO₄).    -   1.9 Kit 1.3-1.8 wherein the one or more bases comprise a metal        citrate salt (e.g., sodium citrate).    -   1.10 Kit 1.9 wherein the kit comprises 1 or 5 mg to 200 or 500        mg of the metal citrate salt (e.g., sodium citrate), e.g., from        about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150,        200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from        about 15, 20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600,        700, 800, 1000, or 1500 mg.    -   1.11 Kit 1.9 wherein the concentration of the metal citrate salt        (e.g., sodium citrate) is 0.01 or 0.1 or 0.5 or 1 or 2 to 250        mM, e.g., from about 0.01 or 0.1 or 0.5 to 1, 2, 5, 10, 15, 20,        25, 40, 50, 60, 75, 100, 125, 150, 175, 200, 250, of 1000 mM,        e.g. from about 1 to 2, 5, 10, 15, 20, 25, 40, 50 or 60 mM,        e.g., from about 5 to 50 mM, e.g., from about 5, 10, 15, 20, 25,        or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about        2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM,        e.g., from about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300,        400, 500, or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about        5, 10, 50, 500, 500, or 1000 mM, e.g., wherein the concentration        of the metal citrate salt (e.g., sodium citrate) is 2 or 3 to 5,        6, 8, 10, 15 or 20 equivalents of Formula II, e.g., about 2.5 or        5 to 10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of the metal citrate salt (e.g., sodium citrate)        is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula III,        e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.12 Kit 1.3-1.11 wherein the one or more bases comprise a metal        phosphate salt (e.g., sodium phosphate, e.g., Na₂HPO₄).    -   1.13 Kit 1.12 wherein the kit comprises 1 or 5 mg to 200 or 500        mg of the metal phosphate salt (e.g., sodium phosphate, e.g.,        Na₂HPO₄), e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30,        40, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 1000,        or 1500 mg, e.g., from about 15, 20, 30, 50, or 100 to 200, 250,        400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.14 Kit 1.12 wherein the concentration of the metal phosphate        salt (e.g., sodium phosphate, e.g., Na₂HPO₄), is 0.01 or 0.1 or        0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to        1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175,        200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25,        40, 50 or 60 mM, e.g., from about 5 to 50 mM, e.g., from about        5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500, or        1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50        to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20,        or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of the metal phosphate salt (e.g.,        sodium phosphate, e.g., Na₂HPO₄) is 2 or 3 to 5, 6, 8, 10, 15 or        20 equivalents of Formula II, e.g., about 2.5 or 5 to 10, e.g.        about 2.5, e.g., about 5, e.g., wherein the concentration of the        metal phosphate salt (e.g., sodium phosphate, e.g., Na₂HPO₄) is        2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula III,        e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.15 Kit 1.3-1.14 wherein the kit comprises Na₂HPO₄.    -   1.16 Kit 1.15 wherein the kit comprises 1 or 5 mg to 200 or 500        mg Na₂HPO₄, e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30,        40, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 1000,        or 1500 mg, e.g., from about 15, 20, 30, 50, or 100 to 200, 250,        400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.17 Kit 1.15 wherein the concentration of Na₂HPO₄ is 0.01 or        0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or        0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150,        175, 200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15,        20, 25, 40, 50 or 60 mM, e.g., from about 5 to 50 mM, e.g., from        about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500,        or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50        to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20,        or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of each of Na₂HPO₄ is 2 or 3 to 5, 6,        8, 10, 15 or 20 equivalents of Formula II, e.g., about 2.5 or 5        to 10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of Na₂HPO₄ is 2 or 3 to 5, 6, 8, 10, 15 or 20        equivalents of Formula III, e.g., about 5 to 10, e.g. about 5,        e.g., about 10.    -   1.18 Kit 1.3-1.17 wherein the one or more bases comprise an        amine and/or a salt thereof (e.g., morpholine, an amino acid        (e.g., arginine), a mono- and/or poly-hydroxyalkylamine, and/or        a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        e.g., any of the preceding wherein a conjugate acid of the amine        and/or salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,        e.g., between about 6, 7, 8, or 9 and 10, e.g., between about 7        and 9, e.g., between about 8 and 9.    -   1.19 Kit 1.18 wherein the kit comprises 1 or 5 mg to 200 or 500        mg of the amine and/or a salt thereof (e.g., morpholine, an        amino (e.g., arginine), a mono- and/or poly-hydroxyalkylamine,        and/or a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]3N, and/or a salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁-s-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        e.g., any of the preceding wherein a conjugate acid of the amine        and/or salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,        e.g., between about 6, 7, 8, or 9 and 10, e.g., between about 7        and 9, e.g., between about 8 and 9, e.g., from about 1 or 5 or        10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300,        350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15, 20,        30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000,        or 1500 mg.    -   1.20 Kit 1.18 wherein the concentration of the amine and/or a        salt thereof (e.g., morpholine, an amino acid (e.g., arginine),        a mono- and/or poly-hydroxyalkylamine, and/or a salt thereof,        e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a        salt thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., any of the        preceding wherein a conjugate acid of the amine and/or salt        thereof has a pKa between 6, 7, 8, 9, or 10 and 11, e.g.,        between about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9,        e.g., between about 8 and 9, is 0.01 or 0.1 or 0.5 or 1 or 2 to        250 mM, e.g., from about 0.01 or 0.1 or 0.5 to 1, 2, 5, 10, 15,        20, 25, 40, 50, 60, 75, 100, 125, 150, 175, 200, 250, or 1000        mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25, 40, 50 or 60 mM,        e.g., from about 5 to 50 mM, e.g., from about 5, 10, 15, 20, 25,        or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about        2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM,        e.g., from about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300,        400, 500, or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about        5, 10, 50, 500, 500, or 1000 mM, e.g., wherein the concentration        of each of the amine and/or a salt thereof (e.g., morpholine, an        amino acid (e.g., arginine), a mono- and/or        poly-hydroxyalkylamine, and/or a salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine) is 2 or 3 to 5, 6,        8, 10, 15 or 20 equivalents of Formula II, e.g., about 2.5 or 5        to 10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of each of the amine and/or a salt thereof (e.g.,        morpholine, an amino acid (e.g., arginine), a mono- and/or        poly-hydroxyalkylamine, and/or a salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine) is 2 or 3 to 5, 6,        8, 10, 15 or 20 equivalents of Formula III, e.g., about 5 to 10,        e.g. about 5, e.g., about 10.    -   1.21 Kit 1.3-1.20 wherein the one or more bases comprise a mono-        and/or poly-hydroxyalkylamine and/or a salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine).    -   1.22 Kit 1.21 wherein the kit comprises 1 or 5 mg to 200 or 500        mg of the mono- and/or poly-hydroxyalkylamine and/or salt        thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N,        and/or a salt thereof wherein each R⁸ is independently C₁₋₈alkyl        (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃)        and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g.,        C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is        —CH₃ and another R⁸ is —(CH₂)₆—) and each n is independently 1-8        (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75,        100, 150, 200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg,        e.g., from about 15, 20, 30, 50, or 100 to 200, 250, 400, 450,        500, 600, 700, 800, 1000, or 1500 mg.    -   1.23 Kit 1.21 wherein the concentration of the mono- and/or        poly-hydroxyalkylamine and/or salt thereof, e.g., (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein        each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), is 0.01 or 0.1 or        0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to        1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175,        200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25,        40, 50 or 60 mM, e.g., from about 5 to 50 mM, e.g., from about        5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500, or        1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50        to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20,        or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of each of the mono- and/or        poly-hydroxyalkylamine and/or salt thereof, e.g., (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein        each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine) is 2 or 3 to 5, 6,        8, 10, 15 or 20 equivalents of Formula II, e.g., about 2.5 or 5        to 10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of the mono- and/or poly-hydroxyalkylamine and/or        salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]3N, and/or a salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C)-6-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine)        agents is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula        III, e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.24 Kit 1.3-1.23 wherein the one or more bases comprise        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]3N, and/or salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine).    -   1.25 Kit 1.24 wherein the kit comprises 1 or 5 mg to 200 or 500        mg of the (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or        salt thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., from about 1        or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250,        300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15,        20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800,        1000, or 1500 mg.    -   1.26 Kit 1.24 wherein the concentration of (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or salt thereof wherein        each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), is 0.01 or 0.1 or        0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to        1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175,        200, 250, of 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25,        40, 50 or 60 mM, e.g., from about 5 to 50 mM, e.g., from about        5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500, or        1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50        to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20,        or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine)        is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula II,        e.g., about 2.5 or 5 to 10, e.g. about 2.5, e.g., about 5, e.g.,        wherein the concentration of (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine)        is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula III,        e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.27 Kit 1.3-1.26 wherein the one or more bases comprise        tris(hydroxymethyl)aminomethane and/or meglumine, e.g,        tris(hydroxymethyl)aminomethane, e.g., meglumine.    -   1.28 Kit 1.27 wherein the kit comprises 1 or 5 mg to 200 or 500        mg tris(hydroxymethyl)aminomethane, e.g., from about 1 or 5 or        10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300,        350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15, 20,        30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000,        or 1500 mg and/or wherein the kit comprises 1 or 5 mg to 200 or        500 mg meglumine, e.g., from about 1 or 5 or 10 mg to 15, 20,        25, 30, 40, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500,        1000, or 1500 mg, e.g., from about 15, 20, 30, 50, or 100 to        200, 250, 400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.29 Kit 1.27 wherein the concentration of a        tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate) is 0.01 or 0.1 or 0.5        or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to 1,        2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175, 200,        250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25, 40,        50 or 60 mM, e.g., from about 5 to 50 mM, e.g., from about 5,        10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500, or 1000        mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50, 500,        500, or 1000 mM.    -   1.30 Kit 1.3-1.29 wherein the one or more bases comprise the        tris(hydroxymethyl)aminomethane salt, e.g.,        tris(hydroxymethyl)aminomethane acetate.    -   1.31 Kit 1.30 wherein the composition comprises 1 or 5 mg to 200        or 500 mg of the tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate), e.g., from about 1 or        5 or 10 mg to 15, 20, 25, 30, 50, 75, 100, 150, 200, 250, 300,        350, 400, 450, 500, 1000, or 1500 mg        tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate), e.g., 1 or 5 mg to 200        or 500 mg tris(hydroxymethyl)aminomethane acetate, e.g., from        about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150,        200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from        about 15, 20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600,        700, 800, 1000, or 1500 mg.    -   1.32 Kit 1.30 wherein the concentration of the        tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate) is 0.01 or 0.1 or 0.5        or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to 1,        2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175, 200,        250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25, 40,        50 or 60 mM, e.g., from about 5 to 50 mM, e.g., from about 5,        10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500, or 1000        mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50, 500,        500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50 to        100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20, or        200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of the tris(hydroxymethyl)aminomethane        salt (e.g., tris(hydroxymethyl)aminomethane acetate) is 2 or 3        to 5, 6, 8, 10, 15 or 20 equivalents of Formula II, e.g., about        2.5 or 5 to 10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of the tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate) is 2 or 3 to 5, 6, 8,        10, 15 or 20 equivalents of Formula III, e.g., about 5 to 10,        e.g. about 5, e.g., about 10.    -   1.33 Kit 1.3-1.32 wherein the one or more bases comprise a base,        e.g., an amine and/or a salt thereof, wherein a conjugate acid        of the base has a pKa between 6, 7, 8, 9, or 10 and 11, e.g.,        between about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9,        e.g., between about 8 and 9.    -   1.34 Kit 1.33 wherein the kit comprises 1 or 5 mg to 200 or 500        mg of the base, e.g., from about 1 or 5 or 10 mg to 15, 20, 25,        30, 40, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500,        1000, or 1500 mg, e.g., from about 15, 20, 30, 50, or 100 to        200, 250, 400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.35 Kit 1.34 wherein the concentration of the base is 0.01 or        0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or        0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150,        175, 200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15,        20, 25, 40, 50 or 60 mM, e.g., from about 5 to 50 mM, e.g., from        about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500,        or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50        to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20,        or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of the base is 2 or 3 to 5, 6, 8, 10,        15 or 20 equivalents of Formula II, e.g., about 2.5 or 5 to 10,        e.g. about 2.5, e.g., about 5, e.g., wherein the concentration        of the base is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of        Formula III, e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.36 Kit 1.3-1.35 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the one or more bases is at least 1:1.    -   1.37 Kit 1.3-1.36 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the one or more bases is at least 1:2,        e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.38 Kit 1.37 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to a metal citrate salt (e.g., sodium        citrate) is at least 1:2, e.g., at least about 1:2, 1:3, 1:4, or        1:5 to 1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at        least about 1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20,        or 1:30, e.g., at least about 1:2.5, e.g., at least about 1:5,        e.g. at least about 1:10.    -   1.39 Kit 1.37 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to a metal phosphate salt (e.g., sodium        phosphate, e.g., Na₂HPO₄) is at least 1:2, e.g., at least about        1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or        1:30, e.g., at least about 1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9,        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5, e.g., at        least about 1:5, e.g. at least about 1:10.    -   1.40 Kit 1.37 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the amine and/or salt thereof (e.g.,        morpholine, amino acid (e.g., arginine), mono- and/or        poly-hydroxyalkylamine, and/or salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., any of the        preceding wherein a conjugate acid of the amine and/or salt        thereof has a pKa between 6, 7, 8, 9, or 10 and 11, e.g.,        between about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9,        e.g., between about 8 and 9, is at least 1:2, e.g., at least        about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to 1:10, 1:15,        1:20, or 1:30, e.g., at least about 1:2.5 to 1:5, 1:6, 1:7, 1:8,        1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5,        e.g., at least about 1:5, e.g. at least about 1:10.    -   1.41 Kit 1.40 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the mono- and/or poly-hydroxyalkylamine        and/or salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        is at least 1:2, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to        1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.42 Kit 1.41 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        is 1:2, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7,        1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to        1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at        least about 1:2.5, e.g., at least about 1:5, e.g. at least about        1:10.    -   1.43 Kit 1.42 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to tris(hydroxymethyl)aminomethane is at        least 1:2, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6,        1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.44 Kit 1.42 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to a tris(hydroxymethyl)aminomethane salt        (e.g., tris(hydroxymethyl)aminomethane acetate) is at least 1:2,        e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.45 Kit 1.37 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to a base, e.g., an amine and/or a salt        thereof, wherein a conjugate acid of the base has a pKa between        6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7, 8, or 9 and        10, e.g., between about 7 and 9, e.g., between about 8 and 9, is        at least 1:2, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6,        1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.46 Kit 1.2-1.45 wherein the kit comprises one or more bulking        agents which may provide an adequate structure to the        lyophilized cake, e.g., one or more of mannitol, lactose,        sucrose, trehalose, sorbitol, glucose, raffinose, arginine,        glycine, histidine, dextran (e.g., dextran 40),        polyvinylpyrrolidone, polyethylene glycol, and polypropylene        glycol, e.g., one or more of mannitol, glucose, sucrose,        lactose, trehalose, and dextran (e.g., dextran 40).    -   1.47 Kit 1.46 wherein the kit comprises 5 or 10 or 50 mg to 2 or        5 g of one or more bulking agents, e.g., from about 50 or 100 mg        to 200, 300, 500, or 800 mg, or 1, 1.5, 2, 3, 4, or 5 g of one        or more bulking agents.    -   1.48 Kit 1.2-1.47 wherein the kit comprises dextran (e.g.,        dextran 40).    -   1.49 Kit 1.48 wherein the kit comprises 5 or 10 or 50 mg to 2 or        5 g dextran (e.g., dextran 40), e.g., from about 50 or 100 mg to        200, 300, 500, or 800 mg, 1, 1.5, 2, 3, 4, or 5 g dextran (e.g.,        dextran 40).    -   1.50 Kit 1.2-1.49 wherein the composition comprises one or more        solubilizing agents, e.g., ethylenediamine tetraacetic acid        (EDTA) or a salt thereof (e.g., calcium disodium EDTA, disodium        EDTA, sodium EDTA), alpha cyclodextrin,        hydroxypropyl-β-cyclodextrin, polysorbate 80, tert-butanol,        isopropanol, dichloromethane, ethanol, acetone, and glycerol;        one or more collapse temperature modifiers which may shift the        overall collapse temperature higher, e.g., one or more of        dextran, Ficoll®, gelatin, and hydroxyethyl starch; one or more        tonicity modifiers, e.g., one or more of sodium chloride,        potassium chloride, sucrose, mannitol, glucose, and lactose; and        one or more antimicrobial agents, e.g., one or more of benzyl        alcohol, phenol, 2-phenoxyethanol, m-cresol, chlorobutanol,        parabens (e.g., methyl paraben, ethyl paraben, propyl paraben),        benzalkonium chloride, benzethonium chloride, myristyl        gamma-picolinium salt (e.g., myristyl gamma-picolinium        chloride), and organomercury compounds and salts (e.g., phenyl        mercuric acetate, phenyl mercuric borate, phenyl mercuric        nitrate, and thimerosal).    -   1.51 Kit 1.2-1.50 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and the one pharmaceutically acceptable        excipients are in the same container or in one or more different        containers.    -   1.52 Kit 1.51 wherein the one or more pharmaceutically        acceptable excipients comprise one or more bases, e.g., a base        wherein upon dissolution of the composition in a solvent, e.g.,        an aqueous solution, e.g., an aqueous solution, the solution has        a pH between 7, 7.5, or 8 and 10.5, e.g., between about 7, 7.5,        or 8 and 9.5, e.g., between about 7 or 7.5 and 8, e.g., between        about 7.5 and 8.5, e.g., about 7.5, e.g., about 8.5, e.g.,        between about 8 and 8.5, e.g., about 8.2, e.g., a base wherein a        conjugate acid of the base has a pKa between 6, 7, 8, 9, or 10        and 11, e.g., between about 6, 7, 8, or 9 and 10, e.g., between        about 7 and 9, e.g., between about 8 and 9, e.g., wherein the        one or more bases are one or more of:        -   a) a C₁₋₈-alkyl mono-, di-, or tri-carboxylic acid salt,            e.g., a citrate salt, e.g, a metal citrate salt (e.g., an            alkali and/or alkaline citrate salt, e.g., an alkali citrate            salt, e.g., sodium citrate and/or potassium citrate), e.g.,            a tartrate salt (e.g., a metal tartrate salt, an alkali            tartrate, e.g., sodium tartrate), e.g., a succinate salt            (e.g., a metal succinate salt, e.g., an alkali succinate,            e.g., disodium succinate), and/or e.g., a lactate salt            (e.g., a metal lactate salt, e.g., an alkali lactate, e.g.,            sodium lactate),        -   b) a phosphate salt, e.g., a metal phosphate salt (e.g., an            alkali and/or alkaline phosphate salt, e.g., an alkali            phosphate salt, e.g., sodium phosphate (e.g., NaH₂PO₄ and/or            Na₂HPO₄) and/or potassium phosphate (e.g., KH₂PO₄ and/or            K₂HPO₄)),        -   c) an amine and/or a salt thereof (e.g., morpholine,            piperazine, benethamine, benzathine, trimethylglycine,            hydrabamine, 4-(2-hydroxyethyl)morpholine,            1-2-hydroxyethyl)-pyrrolidine, an amino acid (e.g., arginine            and/or lysine), a mono- and/or poly-hydroxyalkylamine,            and/or a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,            [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each R⁸ is            independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,            e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene            (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—,            e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is            —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,            5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known            as tris base) and/or a salt thereof (e.g.,            tris(hydroxymethyl)aminomethane acetate (also known as tris            acetate), meglumine, dimethylethanolamine, diethylamine,            diethylethanolamine, and/or diethanolamine), e.g., any of            the preceding wherein a conjugate acid of the amine and/or            salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,            e.g., between about 6, 7, 8, or 9 and 10, e.g., between            about 7 and 9, e.g., between about 8 and 9,        -   d) a metal chloride salt (e.g., zinc chloride),        -   e) an acetate salt, e.g., a metal acetate salt (e.g., an            alkali and/or alkaline acetate salt, e.g., an alkali acetate            salt, e.g., sodium acetate and/or potassium acetate),        -   f) a hydroxide and/or alkoxide salt, e.g., a metal hydroxide            and/or alkoxide salt (e.g., a quarternary ammonium            hydroxide, e.g., ammonium hydroxide and/or choline            hydroxide, lithium hydroxide, aluminum hydroxide, e.g., an            alkali and/or alkaline hydroxide salt, e.g., sodium            hydroxide, potassium hydroxide, calcium hydroxide, magnesium            hydroxide, and/or magnesium ethoxide, e.g., sodium            hydroxide),        -   g) a carbonate and/or bicarbonate salt, e.g., a metal            carbonate and/or metal bicarbonate salt (e.g., an alkali            and/or alkaline carbonate salt, e.g., an alkali and/or            alkaline bicarbonate salt, e.g., sodium bicarbonate), and/or        -   h) a metal borate salt (e.g., an alkali borate salt, e.g.,            sodium borate),    -    e.g., one or more of sodium citrate, Na₂HPO₄,        tris(hydroxymethyl)aminomethane, and a        tris(hydroxymethyl)aminomethane salt (e.g., tris acetate), e.g.,        one or more of sodium citrate, Na₂HPO₄, and        tris(hydroxymethyl)aminomethane, e.g., one or more of sodium        citrate and Na₂HPO₄, e.g., Na₂HPO₄, e.g.,        tris(hydroxymethyl)aminomethane, wherein the one or more bases        are in the same container as        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate or in one or more different containers.    -   1.53 Kit 1.51 or 1.52 wherein the one or more pharmaceutically        acceptable excipients comprise one or more bases, e.g., a base        wherein upon dissolution of the composition in a solvent, e.g.,        an aqueous solution, the solution has a pH between 7, 7.5, or 8        and 10.5, e.g., between about 7, 7.5, or 8 and 9.5, e.g.,        between about 7 or 7.5 and 8, e.g., between about 7.5 and 8.5,        e.g., about 7.5, e.g., about 8.5, e.g., between about 8 and 8.5,        e.g., about 8.2, e.g., a base wherein a conjugate acid of the        base has a pKa between 6, 7, 8, 9, or 10 and 11, e.g., between        about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9, e.g.,        between about 8 and 9, e.g., wherein the one or more bases are        one or more of:        -   a) a metal citrate salt (e.g., an alkali and/or alkaline            citrate salt, e.g., an alkali citrate salt, e.g., sodium            citrate and/or potassium citrate),        -   b) a metal phosphate salt (e.g., an alkali and/or alkaline            phosphate salt, e.g., an alkali phosphate salt, e.g., sodium            phosphate (e.g., NaH₂PO₄ and/or Na₂HPO₄) and/or potassium            phosphate (e.g., KH₂PO₄ and/or K₂HPO₄)),        -   c) an amine and/or a salt thereof (e.g., morpholine, an            amino acid (e.g., arginine), a mono- and/or            poly-hydroxyalkylamine, and/or a salt thereof, e.g.,            (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a            salt thereof wherein each R⁸ is independently C₁₋₈alkyl            (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g.,            —CH₃) and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene,            e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g.,            one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and each n is            independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,            tris(hydroxymethyl)aminomethane (also known as tris base)            and/or a salt thereof (e.g., tris(hydroxymethyl)aminomethane            acetate (also known as tris acetate), meglumine, and/or            diethanolamine), e.g., any of the preceding wherein a            conjugate acid of the amine and/or salt thereof has a pKa            between 6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7,            8, or 9 and 10, e.g., between about 7 and 9, e.g., between            about 8 and 9,        -   d) a metal acetate salt (e.g., an alkali and/or alkaline            acetate salt, e.g., an alkali acetate salt, e.g., sodium            acetate and/or potassium acetate),        -   e) a metal hydroxide salt (e.g., an alkali and/or alkaline            hydroxide salt, e.g., sodium hydroxide, potassium hydroxide,            calcium hydroxide, and/or magnesium hydroxide, e.g., sodium            hydroxide),        -   f) a metal carbonate and/or bicarbonate salt (e.g., an            alkali and/or alkaline carbonate salt, e.g., an alkali            and/or alkaline bicarbonate salt, e.g., sodium bicarbonate),            and/or        -   g) a metal borate salt (e.g., an alkali borate salt, e.g.,            sodium borate),    -    e.g., one or more of sodium citrate, Na₂HPO₄,        tris(hydroxymethyl)aminomethane, and a        tris(hydroxymethyl)aminomethane salt (e.g., tris acetate), e.g.,        one or more of sodium citrate, Na₂HPO₄, and        tris(hydroxymethyl)aminomethane, e.g., one or more of sodium        citrate and Na₂HPO₄, e.g., Na₂HPO₄, e.g.,        tris(hydroxymethyl)aminomethane, wherein the one or more bases        are in the same container as        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate or in one or more different containers.    -   1.54 Kit 1.52 or 1.53 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and one or more of a metal citrate salt        (e.g., sodium citrate) and a metal phosphate salt (e.g., sodium        phosphate, e.g., Na₂HPO₄) are in the same container or in one or        more different containers.    -   1.55 Kit 1.54 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and the metal citrate salt (e.g., sodium        citrate) are in the same container or in different containers.    -   1.56 Kit 1.54 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and the metal phosphate salt (e.g., sodium        phosphate, e.g., Na₂HPO₄) are in the same container or in        different containers.    -   1.57 Kit 1.52 or 1.53 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and one or more of an amine and/or a salt        thereof (e.g., morpholine, an amino acid (e.g., arginine), a        mono- and/or poly-hydroxyalkylamine, and/or a salt thereof,        e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a        salt thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., any of the        preceding wherein a conjugate acid of the amine and/or salt        thereof has a pKa between 6, 7, 8, 9, or 10 and 11, e.g.,        between about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9,        e.g., between about 8 and 9, are in the same container or in        different containers.    -   1.58 Kit 1.57 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and one or more of a mono- and/or        poly-hydroxyalkylamine and/or a salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]3N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine) are in the same        container or in different containers.    -   1.59 Kit 1.58 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and one or more of (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]3N, and/or salt thereof wherein        each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine) are in the same        container or in different containers.    -   1.60 Kit 1.59 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and tris(hydroxymethyl)aminomethane are in        the same container or in different containers.    -   1.61 Kit 1.59 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and tris(hydroxymethyl)aminomethane acetate        are in the same container or in different containers.    -   1.62 Kit 1.53 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and a base, e.g., an amine and/or a salt        thereof, wherein a conjugate acid of the base has a pKa between        6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7, 8, or 9 and        10, e.g., between about 7 and 9, e.g., between about 8 and 9,        are in the same container or in different containers.    -   1.63 Kit 1.51-1.62 wherein the kit comprises one or more bulking        agents, e.g., one or more of mannitol, lactose, sucrose,        trehalose, sorbitol, glucose, raffinose, arginine, glycine,        histidine, dextran (e.g., dextran 40), polyvinylpyrrolidone,        polyethylene glycol, and polypropylene glycol, e.g., one or more        of mannitol, glucose, sucrose, lactose, trehalose, and dextran        (e.g., dextran 40), wherein the one or more bulking agents are        in the same container as        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate or any other component of the kit or in one        or more different containers.    -   1.64 Kit 1.63 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and dextran (e.g., dextran 40) are in the        same container or in different containers.    -   1.65 Kit 1.51-1.64 wherein the kit comprises one or more        solubilizing agents, e.g., ethylenediamine tetraacetic acid        (EDTA) or a salt thereof (e.g., calcium disodium EDTA, disodium        EDTA, sodium EDTA), alpha cyclodextrin,        hydroxypropyl-β-cyclodextrin, polysorbate 80, tert-butanol,        isopropanol, dichloromethane, ethanol, acetone, and glycerol;        one or more collapse temperature modifiers, e.g., one or more of        dextran, Ficoll®, gelatin, and hydroxyethyl starch; one or more        tonicity modifiers, e.g., one or more of sodium chloride,        potassium chloride, sucrose, mannitol, glucose, and lactose; and        one or more antimicrobial agents, e.g., one or more of benzyl        alcohol, phenol, 2-phenoxyethanol, m-cresol, chlorobutanol,        parabens (e.g., methyl paraben, ethyl paraben, propyl paraben),        benzalkonium chloride, benzethonium chloride, myristyl        gamma-picolinium salt (e.g., myristyl gamma-picolinium        chloride), and organomercury compounds and salts (e.g., phenyl        mercuric acetate, phenyl mercuric borate, phenyl mercuric        nitrate, and thimerosal), wherein the one or more solubilizing        agents, collapse temperature modifiers, tonicity modifiers, and        antimicrobial agents are in the same container as        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate or any other component of the kit or in one        or more different containers, e.g., in any combination in any        number of different containers.    -   1.66 Kit I or 1.1-1.65 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is crystalline.    -   1.67 Kit I or 1.1-1.65 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is amorphous.    -   1.68 Kit I or 1.1-1.65 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is lyophilized, e.g., by freezing, primary        drying, and secondary drying.    -   1.69 Kit 1.2-1.68 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and the one or more pharmaceutically        acceptable excipients are lyophilized.    -   1.70 Kit I or 1.1-1.69 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is suitable for constitution, or        reconstitution if lyophilized, with a solvent, e.g., an aqueous        solution, into a pharmaceutically acceptable liquid (e.g., a        solution or suspension, e.g., a solution).    -   1.71 Kit I or 1.1-1.70 wherein the kit comprises a solvent,        e.g., a sterile solution, e.g., sterile water for injection, a        sterile solution comprising dextrose (e.g., dextrose injection        5%), a sterile solution comprising sodium chloride (e.g., 0.9%        sodium chloride injection), a sterile solution comprising benzyl        alcohol (e.g., bacteriostatic water for injection with benzyl        alcohol or bacteriostatic sodium chloride for injection with        benzyl alcohol), or Lactated Ringer's.    -   1.72 Kit I or 1.1-1.71 wherein the kit comprises 0.5 to 500 mL        solvent, e.g., an aqueous solution, e.g., from about 1 or 2 mL        to 500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 30, 35, 50,        75, 100, 150, 200, 300 or 500 mL, e.g., from about 1 or 2 mL to        5, 10, 25, 50, 75, 100, or 200 mL, e.g., from about 3.5 or 5 to        10, 25, 50, or 100 mL, e.g., about 3.5 or 35 mL.    -   1.73 Kit I or 1.1-1.72 wherein the kit comprises 0.5 to 500 mL        sterile solution, e.g., sterile water for injection, a sterile        solution comprising dextrose (e.g., dextrose injection 5%), a        sterile solution comprising sodium chloride (e.g., 0.9% sodium        chloride injection), a sterile solution comprising benzyl        alcohol (e.g., bacteriostatic water for injection with benzyl        alcohol or bacteriostatic sodium chloride for injection with        benzyl alcohol), or Lactated Ringer's, e.g., from about 1 or 2        mL to 500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 50, 75,        100, 150, 200, 300 or 500 mL, e.g., from about 1 or 2 mL to 5,        10, 25, 30, 35, 50, 75, 100, or 200 mL, e.g., from about 3.5 or        5 to 10, 25, 50, or 100 mL, e.g., about 3.5 or 35 mL.    -   1.74 Kit I or 1.1-1.73 wherein the kit comprises sterile water        for injection or a sterile solution comprising sodium chloride        (e.g., 0.9% sodium chloride injection).    -   1.75 Kit 1.74 wherein the kit comprises 0.5 to 500 mL sterile        water for injection, e.g., from about 1 or 2 mL to 500 mL, e.g.,        from about 1 or 2 mL to 5, 10, 25, 30, 35, 50, 75, 100, 150,        200, 300 or 500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 50,        75, 100, or 200 mL, e.g., from about 3.5 or 5 to 10, 25, 50, or        100 mL, e.g., about 3.5 or 35 mL.    -   1.76 Kit I or 1.1-1.75 wherein the kit comprises sterile        solution comprising sodium chloride (e.g., 0.9% sodium chloride        injection).    -   1.77 Kit 1.76 wherein the kit comprises 0.5 to 500 mL of a        sterile solution comprising sodium chloride (e.g., 0.9% sodium        chloride injection), e.g., from about 1 or 2 mL to 500 mL, e.g.,        from about 1 or 2 mL to 5, 10, 25, 50, 75, 100, 150, 200, 300 or        500 mL, e.g., from about 1 or 2 mL to 5, 10, 25, 30, 35, 50, 75,        100, or 200 mL, e.g., from about 3.5 or 5 to 10, 25, 50, or 100        mL, e.g., about 3.5 or 35 mL.    -   1.78 Kit 1.71-1.77 wherein the solvent, e.g., the sterile        solution, comprises one or more bases, e.g., a base wherein upon        dissolution of the composition in a solvent, e.g., an aqueous        solution, the solution has a pH between 7, 7.5, or 8 and 10.5,        e.g., between about 7, 7.5, or 8 and 9.5, e.g., between about 7        or 7.5 and 8, e.g., between about 7.5 and 8.5, e.g., about 7.5,        e.g., about 8.5, e.g., between about 8 and 8.5, e.g., about 8.2,        e.g., a base wherein a conjugate acid of the base has a pKa        between 6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7, 8,        or 9 and 10, e.g., between about 7 and 9, e.g., between about 8        and 9, e.g., wherein the one or more bases are one or more of:        -   a) a C₁₋₈-alkyl mono-, di-, or tri-carboxylic acid salt,            e.g., a citrate salt, e.g, a metal citrate salt (e.g., an            alkali and/or alkaline citrate salt, e.g., an alkali citrate            salt, e.g., sodium citrate and/or potassium citrate), e.g.,            a tartrate salt (e.g., a metal tartrate salt, an alkali            tartrate, e.g., sodium tartrate), e.g., a succinate salt            (e.g., a metal succinate salt, e.g., an alkali succinate,            e.g., disodium succinate), and/or e.g., a lactate salt            (e.g., a metal lactate salt, e.g., an alkali lactate, e.g.,            sodium lactate),        -   b) a phosphate salt, e.g., a metal phosphate salt (e.g., an            alkali and/or alkaline phosphate salt, e.g., an alkali            phosphate salt, e.g., sodium phosphate (e.g., NaH₂PO₄ and/or            Na₂HPO₄) and/or potassium phosphate (e.g., KH₂PO₄ and/or            K₂HPO₄)),        -   c) an amine and/or a salt thereof (e.g., morpholine,            piperazine, benethamine, benzathine, trimethylglycine,            hydrabamine, 4-(2-hydroxyethyl)morpholine,            1-2-hydroxyethyl)-pyrrolidine, an amino acid (e.g., arginine            and/or lysine), a mono- and/or poly-hydroxyalkylamine,            and/or a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,            [(HO)_(n)R⁸]3N, and/or a salt thereof wherein each R⁸ is            independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,            e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene            (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—,            e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is            —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,            5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known            as tris base) and/or a salt thereof (e.g.,            tris(hydroxymethyl)aminomethane acetate (also known as tris            acetate), meglumine, dimethylethanolamine, diethylamine,            diethylethanolamine, and/or diethanolamine), e.g., any of            the preceding wherein a conjugate acid of the amine and/or            salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,            e.g., between about 6, 7, 8, or 9 and 10, e.g., between            about 7 and 9, e.g., between about 8 and 9,        -   d) a metal chloride salt (e.g., zinc chloride),        -   e) an acetate salt, e.g., a metal acetate salt (e.g., an            alkali and/or alkaline acetate salt, e.g., an alkali acetate            salt, e.g., sodium acetate and/or potassium acetate),        -   f) a hydroxide and/or alkoxide salt, e.g., a metal hydroxide            and/or alkoxide salt (e.g., a quarternary ammonium            hydroxide, e.g., ammonium hydroxide and/or choline            hydroxide, lithium hydroxide, aluminum hydroxide, e.g., an            alkali and/or alkaline hydroxide salt, e.g., sodium            hydroxide, potassium hydroxide, calcium hydroxide, magnesium            hydroxide, and/or magnesium ethoxide, e.g., sodium            hydroxide),        -   g) a carbonate and/or bicarbonate salt, e.g., a metal            carbonate and/or metal bicarbonate salt (e.g., an alkali            and/or alkaline carbonate salt, e.g., an alkali and/or            alkaline bicarbonate salt, e.g., sodium bicarbonate), and/or        -   h) a metal borate salt (e.g., an alkali borate salt, e.g.,            sodium borate),    -    e.g., one or more of sodium citrate, Na₂HPO₄,        tris(hydroxymethyl)aminomethane, and a        tris(hydroxymethyl)aminomethane salt (e.g., tris acetate), e.g.,        one or more of sodium citrate, Na₂HPO₄, and        tris(hydroxymethyl)aminomethane, e.g., one or more of sodium        citrate and Na₂HPO₄, e.g., Na₂HPO₄, e.g.,        tris(hydroxymethyl)aminomethane.    -   1.79 Kit 1.71-1.78 wherein the solvent, e.g., the sterile        solution, comprises one or more pharmaceutically acceptable        bases, e.g., one or more bases wherein upon dissolution of the        composition in a solvent the solution has a pH between 7, 7.5,        or 8 and 10.5, e.g., between about 7, 7.5, or 8 and 9.5, e.g.,        between about 7 or 7.5 and 8, e.g., between about 7.5 and 8.5,        e.g., about 7.5, e.g., about 8.5, e.g., between about 8 and 8.5,        e.g., about 8.2, e.g., a base wherein a conjugate acid of the        base has a pKa between 6, 7, 8, 9, or 10 and 11, e.g., between        about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9, e.g.,        between about 8 and 9, e.g., wherein the one or more base are        one or more of:        -   a) a metal citrate salt (e.g., an alkali and/or alkaline            citrate salt, e.g., an alkali citrate salt, e.g., sodium            citrate and/or potassium citrate),        -   b) a metal phosphate salt (e.g., an alkali and/or alkaline            phosphate salt, e.g., an alkali phosphate salt, e.g., sodium            phosphate (e.g., NaH₂PO₄ and/or Na₂HPO₄) and/or potassium            phosphate (e.g., KH₂PO₄ and/or K₂HPO₄)),        -   c) an amine and/or a salt thereof (e.g., morpholine, an            amino acid (e.g., arginine), a mono- and/or            poly-hydroxyalkylamine, and/or a salt thereof, e.g.,            (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a            salt thereof wherein each R⁸ is independently C₁₋₈alkyl            (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g.,            —CH₃) and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene,            e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g.,            one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and each n is            independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,            tris(hydroxymethyl)aminomethane (also known as tris base)            and/or a salt thereof (e.g., tris(hydroxymethyl)aminomethane            acetate (also known as tris acetate), meglumine, and/or            diethanolamine), e.g., any of the preceding wherein a            conjugate acid of the amine and/or salt thereof has a pKa            between 6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7,            8, or 9 and 10, e.g., between about 7 and 9, e.g., between            about 8 and 9,        -   d) a metal acetate salt (e.g., an alkali and/or alkaline            acetate salt, e.g., an alkali acetate salt, e.g., sodium            acetate and/or potassium acetate),        -   e) a metal hydroxide salt (e.g., an alkali and/or alkaline            hydroxide salt, e.g., sodium hydroxide, potassium hydroxide,            calcium hydroxide, and/or magnesium hydroxide, e.g., sodium            hydroxide),        -   f) a metal carbonate and/or bicarbonate salt (e.g., an            alkali and/or alkaline carbonate salt, e.g., an alkali            and/or alkaline bicarbonate salt, e.g., sodium bicarbonate),            and/or        -   g) a metal borate salt (e.g., an alkali borate salt, e.g.,            sodium borate),    -    e.g., one or more of sodium citrate, Na₂HPO₄,        tris(hydroxymethyl)aminomethane, and a        tris(hydroxymethyl)aminomethane salt (e.g., tris acetate), e.g.,        one or more of sodium citrate, Na₂HPO₄, and        tris(hydroxymethyl)aminomethane, e.g., one or more of sodium        citrate and Na₂HPO₄, e.g., Na₂HPO₄, e.g.,        tris(hydroxymethyl)aminomethane.    -   1.80 Kit 1.78 or 1.79 wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of the base,        e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75,        100, 150, 200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg,        e.g., from about 15, 20, 30, 50, or 100 to 200, 250, 400, 450,        500, 600, 700, 800, 1000, or 1500 mg.    -   1.81 Kit 1.78 or 1.79 wherein the concentration of each of the        one or more bases is 0.01 or 0.1 or 0.5 or 1 or 2 to 250 mM,        e.g., from about 0.01 or 0.1 or 0.5 to 1, 2, 5, 10, 15, 20, 25,        40, 50, 60, 75, 100, 125, 150, 175, 200, 250, or 1000 mM, e.g.        from about 1 to 2, 5, 10, 15, 20, 25, 40, 50 or 60 mM, e.g.,        from about 5 to 50 mM, e.g., from about 5, 10, 15, 20, 25, or 50        to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20,        or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        from about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400,        500, or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5,        10, 50, 500, 500, or 1000 mM, e.g., wherein the concentration of        each of the one or more bases is 2 or 3 to 5, 6, 8, 10, 15 or 20        equivalents of Formula II, e.g., about 2.5 or 5 to 10, e.g.        about 2.5, e.g., about 5, e.g., wherein the concentration of        each of the one or more bases is 2 or 3 to 5, 6, 8, 10, 15 or 20        equivalents of Formula III, e.g., about 5 to 10, e.g. about 5,        e.g., about 10.    -   1.82 Kit 1.78-1.81 wherein the solvent, e.g. the sterile        solution, comprises one or more of a metal citrate salt (e.g.,        sodium citrate) and a metal phosphate salt (e.g., sodium        phosphate, e.g., Na₂HPO₄).    -   1.83 Kit 1.78-1.82 wherein the solvent, e.g. the sterile        solution, comprises a metal citrate salt (e.g., sodium citrate).    -   1.84 Kit 1.83 wherein the solvent, e.g., the sterile solution,        comprises 1 or 5 mg to 200 mg or 500 mg of the metal citrate        salt (e.g., sodium citrate), e.g., from about 1 or 5 mg to 200        or 500 mg, e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30,        40, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 1000,        or 1500 mg, e.g., from about 15, 20, 30, 50, or 100 to 200, 250,        400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.85 Kit 1.83 wherein the concentration of the metal citrate        salt (e.g., sodium citrate) is from about 0.01 or 0.1 or 0.5 or        1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to 1, 2,        5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175, 200, 250,        or 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25, 40, 50 or        60 mM, e.g., from about 5 to 50 mM, e.g., from about 5, 10, 15,        20, 25, or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g.,        about 2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000        mM, e.g., from about 5, 10, 15, 20, 25, or 50 to 100, 200, 250,        300, 400, 500, or 1000 mM, e.g., about 2, 20, or 200 mM, e.g.,        about 5, 10, 50, 500, 500, or 1000 mM, e.g., wherein the        concentration of the metal citrate salt (e.g., sodium citrate)        is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula II,        e.g., about 2.5 or 5 to 10, e.g. about 2.5, e.g., about 5, e.g.,        wherein the concentration of the metal citrate salt (e.g.,        sodium citrate) is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents        of Formula III, e.g., about 5 to 10, e.g. about 5, e.g., about        10.    -   1.86 Kit 1.78-1.85 wherein the solvent, e.g., the sterile        solution, comprises a metal phosphate salt (e.g., sodium        phosphate, e.g., Na₂HPO₄).    -   1.87 Kit 1.86 wherein the solvent, e.g., the sterile solution,        comprises 1 or 5 mg to 200 mg or 500 mg of the metal phosphate        salt (e.g., sodium phosphate, e.g., Na₂HPO₄), e.g., from about 1        or 5 mg to 200 or 500 mg, e.g., from about 1 or 5 or 10 mg to        15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300, 350, 400,        450, 500, 1000, or 1500 mg, e.g., from about 15, 20, 30, 50, or        100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000, or 1500 mg.    -   1.88 Kit 1.86 wherein the concentration of the metal phosphate        salt (e.g., sodium phosphate, e.g., Na₂HPO₄), is from 0.01 or        0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or        0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150,        175, 200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15,        20, 25, 40, 50 or 60 mM, e.g., from about 5 to 50 mM, e.g., from        about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500,        or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50        to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20,        or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of each of the metal phosphate salt        (e.g., sodium phosphate, e.g., Na₂HPO₄) is 2 or 3 to 5, 6, 8,        10, 15 or 20 equivalents of Formula II, e.g., about 2.5 or 5 to        10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of the metal phosphate salt (e.g., sodium        phosphate, e.g., Na₂HPO₄) is 2 or 3 to 5, 6, 8, 10, 15 or 20        equivalents of Formula III, e.g., about 5 to 10, e.g. about 5,        e.g., about 10.    -   1.89 Kit 1.78-1.88 wherein the wherein the solvent, e.g., the        sterile solution, comprises Na₂HPO₄.    -   1.90 Kit 1.89 wherein the solvent, e.g., the sterile solution,        comprises 1 or 5 mg to 200 or 500 mg Na₂HPO₄, e.g., from about 1        or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250,        300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15,        20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800,        1000, or 1500 mg.    -   1.91 Kit 1.89 wherein the concentration of Na₂HPO₄ is 0.01 or        0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or        0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150,        175, 200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15,        20, 25, 40, 50 or 60 mM, e.g., from about 5 to 50 mM, e.g., from        about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500,        or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50        to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20,        or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of Na₂HPO₄ is 2 or 3 to 5, 6, 8, 10,        15 or 20 equivalents of Formula II, e.g., about 2.5 or 5 to 10,        e.g. about 2.5, e.g., about 5, e.g., wherein the concentration        of Na₂HPO₄ is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of        Formula III, e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.92 Kit 1.78-1.91 wherein the solvent, e.g., the sterile        solution, comprises an amine and/or a salt thereof (e.g.,        morpholine, an amino acid (e.g., arginine), a mono- and/or        poly-hydroxyalkylamine, and/or a salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., any of the        preceding wherein a conjugate acid of the amine and/or salt        thereof has a pKa between 6, 7, 8, 9, or 10 and 11, e.g.,        between about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9,        e.g., between about 8 and 9.    -   1.93 Kit 1.92 wherein the wherein the solvent, e.g., the sterile        solution, comprises 1 or 5 mg to 200 or 500 mg of the amine        and/or a salt thereof (e.g., morpholine, an amino acid (e.g.,        arginine), a mono- and/or poly-hydroxyalkylamine, and/or a salt        thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N,        and/or a salt thereof wherein each R⁸ is independently C₁₋₈alkyl        (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃)        and n is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g.,        C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is        —CH₃ and another R⁸ is —(CH₂)₆—) and each n is independently 1-8        (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        e.g., any of the preceding wherein a conjugate acid of the amine        and/or salt thereof has a pKa between 6, 7, 8, 9, or 10 and 11,        e.g., between about 6, 7, 8, or 9 and 10, e.g., between about 7        and 9, e.g., between about 8 and 9, e.g., from about 1 or 5 or        10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300,        350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15, 20,        30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000,        or 1500 mg.    -   1.94 Kit 1.92 wherein the concentration of the amine and/or a        salt thereof (e.g., morpholine, an amino acid (e.g., arginine),        a mono- and/or poly-hydroxyalkylamine, and/or a salt thereof,        e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a        salt thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁-s-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., any of the        preceding wherein a conjugate acid of the amine and/or salt        thereof has a pKa between 6, 7, 8, 9, or 10 and 11, e.g.,        between about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9,        e.g., between about 8 and 9, is 0.01 or 0.1 or 0.5 or 1 or 2 to        250 mM, e.g., from about 0.01 or 0.1 or 0.5 to 1, 2, 5, 10, 15,        20, 25, 40, 50, 60, 75, 100, 125, 150, 175, 200, 250, or 1000        mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25, 40, 50 or 60 mM,        e.g., from about 5 to 50 mM, e.g., from about 5, 10, 15, 20, 25,        or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about        2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM,        e.g., from about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300,        400, 500, or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about        5, 10, 50, 500, 500, or 1000 mM, e.g., wherein the concentration        of the amine and/or a salt thereof (e.g., morpholine, an amino        acid a (e.g., arginine), a mono- and/or poly-hydroxyalkylamine,        and/or a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine)        is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula II,        e.g., about 2.5 or 5 to 10, e.g. about 2.5, e.g., about 5, e.g.,        wherein the concentration of the amine and/or a salt thereof        (e.g., morpholine, an amino acid (e.g., arginine), a mono-        and/or poly-hydroxyalkylamine, and/or a salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine) is 2 or 3 to 5, 6,        8, 10, 15 or 20 equivalents of Formula III, e.g., about 5 to 10,        e.g. about 5, e.g., about 10.    -   1.95 Kit 1.78-1.94 wherein the solvent, e.g., the sterile        solution, comprises a mono- and/or poly-hydroxyalkylamine and/or        a salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or Cis-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine).    -   1.96 Kit 1.95 wherein the solvent, e.g., the sterile solution,        comprises 1 or 5 mg to 200 or 500 mg of the mono- and/or        poly-hydroxyalkylamine and/or salt thereof, e.g., (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein        each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₈-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C-s-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., from about 1        or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250,        300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15,        20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800,        1000, or 1500 mg.    -   1.97 Kit 1.95 wherein the concentration of the mono- and/or        poly-hydroxyalkylamine and/or salt thereof, e.g., (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein        each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), is 0.01 or 0.1 or        0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to        1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175,        200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25,        40, 50 or 60 mM, e.g., from about 5 to 50 mM, e.g., from about        5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500, or        1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50        to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20,        or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of each of the mono- and/or        poly-hydroxyalkylamine and/or salt thereof, e.g., (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein        each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine) is 2 or 3 to 5, 6,        8, 10, 15 or 20 equivalents of Formula II, e.g., about 2.5 or 5        to 10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of the mono- and/or poly-hydroxyalkylamine and/or        salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or a salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine)        is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula III,        e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.98 Kit 1.78-1.97 wherein the solvent, e.g., the sterile        solution, comprises (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine).    -   1.99 Kit 1.98 wherein the solvent, e.g., the sterile solution,        comprises 1 or 5 mg to 200 or 500 mg of the (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or salt thereof wherein        each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., from about 1        or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250,        300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from about 15,        20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800,        1000, or 1500 mg.    -   1.100 Kit 1.98 wherein the concentration of the (HO)_(n)R⁸NH₂,        [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or salt thereof wherein        each R⁸ is independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g.,        C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or        C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g.,        —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸        is —(CH₂)₆—) and each n is independently 1-8 (e.g., 1, 2, 3, 4,        5, or 6), e.g., tris(hydroxymethyl)aminomethane (also known as        tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), is 0.01 or 0.1 or        0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to        1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175,        200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25,        40, 50 or 60 mM, e.g., from about 5 to 50 mM, e.g., from about        5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500, or        1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50        to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20,        or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of the (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine)        is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula II,        e.g., about 2.5 or 5 to 10, e.g. about 2.5, e.g., about 5, e.g.,        wherein the concentration of the (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]3N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C-s-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine)        is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of Formula III,        e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.101 Kit 1.78-1.100 wherein the solvent, e.g., the sterile        solution, comprises tris(hydroxymethyl)aminomethane.    -   1.102 Kit 1.101 wherein the solvent, e.g., the sterile solution,        comprises 1 or 5 mg to 200 or 500 mg        tris(hydroxymethyl)aminomethane, e.g., from about 1 or 5 or 10        mg to 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300, 350,        400, 450, 500, 1000, or 1500 mg, e.g., from about 15, 20, 30,        50, or 100 to 200, 250, 400, 450, 500, 600, 700, 800, 1000, or        1500 mg.    -   1.103 Kit 1.101 wherein the concentration of        tris(hydroxymethyl)aminomethane is 0.01 or 0.1 or 0.5 or 1 or 2        to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to 1, 2, 5, 10,        15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175, 200, 250, or        1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25, 40, 50 or 60        mM, e.g., from about 5 to 50 mM, e.g., from about 5, 10, 15, 20,        25, or 50 to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g.,        about 2, 20, or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000        mM, e.g., from about 5, 10, 15, 20, 25, or 50 to 100, 200, 250,        300, 400, 500, or 1000 mM, e.g., about 2, 20, or 200 mM, e.g.,        about 5, 10, 50, 500, 500, or 1000 mM, e.g., wherein the        concentration of tris(hydroxymethyl)aminomethane is 2 or 3 to 5,        6, 8, 10, 15 or 20 equivalents of Formula II, e.g., about 2.5 or        5 to 10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of tris(hydroxymethyl)aminomethane is 2 or 3 to 5,        6, 8, 10, 15 or 20 equivalents of Formula III, e.g., about 5 to        10, e.g. about 5, e.g., about 10.    -   1.104 Kit 1.78-1.103 wherein the solvent, e.g., the sterile        solution, comprises a tris(hydroxymethyl)aminomethane salt,        e.g., tris(hydroxymethyl)aminomethane acetate.    -   1.105 Kit 1.104 wherein the solvent, e.g., the sterile solution,        comprises 1 or 5 mg to 200 or 500 mg of the        tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate), e.g., from about 1 or        5 or 10 mg to 15, 20, 25, 30, 40, 50, 75 100, 150, 200, 250,        300, 350, 400, 450, or 500 mg tris(hydroxymethyl)aminomethane        salt (e.g., tris(hydroxymethyl)aminomethane acetate), e.g., 1 or        5 mg to 200 or 500 mg tris(hydroxymethyl)aminomethane acetate,        e.g., from about 1 or 5 or 10 mg to 15, 20, 25, 30, 50, 75, 100,        150, 200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg, e.g.,        from about 15, 20, 30, 50, or 100 to 200, 250, 400, 450, 500,        600, 700, 800, 1000, or 1500 mg.    -   1.106 Kit 1.105 wherein the concentration of the        tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate) is 0.01 or 0.1 or 0.5        or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or 0.5 to 1,        2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150, 175, 200,        250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15, 20, 25, 40,        50 or 60 mM, e.g., from about 5 to 50 mM, e.g., from about 5,        10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500, or 1000        mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50, 500,        500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50 to        100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20, or        200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of the tris(hydroxymethyl)aminomethane        salt (e.g., tris(hydroxymethyl)aminomethane acetate) is 2 or 3        to 5, 6, 8, 10, 15 or 20 equivalents of Formula II, e.g., about        2.5 or 5 to 10, e.g. about 2.5, e.g., about 5, e.g., wherein the        concentration of the tris(hydroxymethyl)aminomethane salt (e.g.,        tris(hydroxymethyl)aminomethane acetate) is 2 or 3 to 5, 6, 8,        10, 15 or 20 equivalents of Formula III, e.g., about 5 to 10,        e.g. about 5, e.g., about 10.    -   1.107 Kit 1.78-1.106 wherein the solvent, e.g., the sterile        solution, comprises a base, e.g., an amine and/or a salt        thereof, wherein a conjugate acid of the base has a pKa between        6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7, 8, or 9 and        10, e.g., between about 7 and 9, e.g., between about 8 and 9.    -   1.108 Kit 1.107 wherein the solvent, e.g., the sterile solution,        comprises 1 or 5 mg to 200 or 500 mg of the base, e.g., from        about 1 or 5 or 10 mg to 15, 20, 25, 30, 40, 50, 75, 100, 150,        200, 250, 300, 350, 400, 450, 500, 1000, or 1500 mg, e.g., from        about 15, 20, 30, 50, or 100 to 200, 250, 400, 450, 500, 600,        700, 800, 1000, or 1500 mg.    -   1.109 Kit 1.107 wherein the concentration of the base is 0.01 or        0.1 or 0.5 or 1 or 2 to 250 mM, e.g., from about 0.01 or 0.1 or        0.5 to 1, 2, 5, 10, 15, 20, 25, 40, 50, 60, 75, 100, 125, 150,        175, 200, 250, or 1000 mM, e.g. from about 1 to 2, 5, 10, 15,        20, 25, 40, 50 or 60 mM, e.g., from about 5 to 50 mM, e.g., from        about 5, 10, 15, 20, 25, or 50 to 100, 200, 250, 300, 400, 500,        or 1000 mM, e.g., about 2, 20, or 200 mM, e.g., about 5, 10, 50,        500, 500, or 1000 mM, e.g., from about 5, 10, 15, 20, 25, or 50        to 100, 200, 250, 300, 400, 500, or 1000 mM, e.g., about 2, 20,        or 200 mM, e.g., about 5, 10, 50, 500, 500, or 1000 mM, e.g.,        wherein the concentration of the base is 2 or 3 to 5, 6, 8, 10,        15 or 20 equivalents of Formula II, e.g., about 2.5 or 5 to 10,        e.g. about 2.5, e.g., about 5, e.g., wherein the concentration        of the base is 2 or 3 to 5, 6, 8, 10, 15 or 20 equivalents of        Formula III, e.g., about 5 to 10, e.g. about 5, e.g., about 10.    -   1.110 Kit 1.78-1.109 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the one or more bases is at least 1:1.    -   1.111 Kit 1.78-1.110 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the one or more bases is at least 1:2, e        e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.112 Kit 1.111 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to a metal citrate salt (e.g., sodium        citrate) is at least 1:2, e.g., at least about 1:2, 1:3, 1:4, or        1:5 to 1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at        least about 1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20,        or 1:30, e.g., at least about 1:2.5, e.g., at least about 1:5,        e.g. at least about 1:10.    -   1.113 Kit 1.111 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to a metal phosphate salt (e.g., sodium        phosphate, e.g., Na₂HPO₄) is at least 1:2, e.g., at least about        1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or        1:30, e.g., at least about 1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9,        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5, e.g., at        least about 1:5, e.g. at least about 1:10.    -   1.114 Kit 1.111 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the amine and/or salt thereof (e.g.,        morpholine, amino acid (e.g., arginine), mono- and/or        poly-hydroxyalkylamine, and/or salt thereof, e.g.,        (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N, and/or salt        thereof wherein each R⁸ is independently C₁₋₈alkyl (e.g.,        C₁₋₆-alkyl, e.g., C₁₋₄-alkyl, e.g., —CH₂CH₃, e.g., —CH₃) and n        is 0 or C₁₋₈-alkylene (e.g., C₁₋₆-alkylene, e.g., C₁₋₄-alkylene,        e.g., —CH₂—CH₂—, e.g., —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and        another R⁸ is —(CH₂)₆—) and each n is independently 1-8 (e.g.,        1, 2, 3, 4, 5, or 6), e.g., tris(hydroxymethyl)aminomethane        (also known as tris base) and/or a salt thereof (e.g.,        tris(hydroxymethyl)aminomethane acetate (also known as tris        acetate), meglumine, and/or diethanolamine), e.g., any of the        preceding wherein a conjugate acid of the amine and/or salt        thereof has a pKa between 6, 7, 8, 9, or 10 and 11, e.g.,        between about 6, 7, 8, or 9 and 10, e.g., between about 7 and 9,        e.g., between about 8 and 9, is at least 1:2, e.g., at least        about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to 1:10, 1:15,        1:20, or 1:30, e.g., at least about 1:2.5 to 1:5, 1:6, 1:7, 1:8,        1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5,        e.g., at least about 1:5, e.g. at least about 1:10.    -   1.115 Kit 1.114 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the mono- and/or poly-hydroxyalkylamine        and/or salt thereof, e.g., (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        is at least 1:2, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to        1:6, 1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.116 Kit 1.115 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH,        [(HO)_(n)R⁸]₃N, and/or salt thereof wherein each R⁸ is        independently C₁₋₈alkyl (e.g., C₁₋₆-alkyl, e.g., C₁₋₄-alkyl,        e.g., —CH₂CH₃, e.g., —CH₃) and n is 0 or C₁₋₈-alkylene (e.g.,        C₁₋₆-alkylene, e.g., C₁₋₄-alkylene, e.g., —CH₂—CH₂—, e.g.,        —C(CH₂)₃—, e.g., one R⁸ is —CH₃ and another R⁸ is —(CH₂)₆—) and        each n is independently 1-8 (e.g., 1, 2, 3, 4, 5, or 6), e.g.,        tris(hydroxymethyl)aminomethane (also known as tris base) and/or        a salt thereof (e.g., tris(hydroxymethyl)aminomethane acetate        (also known as tris acetate), meglumine, and/or diethanolamine),        is 1:2, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7,        1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to        1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at        least about 1:2.5, e.g., at least about 1:5, e.g. at least about        1:10.    -   1.117 Kit 1.116 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to tris(hydroxymethyl)aminomethane is at        least 1:2, e.g., at least about 1:2, 1:3, 1:4, 1:5, 1:6, 1:7,        1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:3, 1:4,        1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at        least about 1:10.    -   1.118 Kit 1.116 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to the tris(hydroxymethyl)aminomethane salt        (e.g., tris(hydroxymethyl)aminomethane acetate) is at least 1:2,        e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6, 1:7, 1:8 to        1:10, 1:15, 1:20, or 1:30, e.g., at least about 1:2.5 to 1:5,        1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30, e.g., at least        about 1:2.5, e.g., at least about 1:5, e.g. at least about 1:10.    -   1.119 Kit 1.111 wherein the molar ratio of        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to a base, e.g., an amine and/or a salt        thereof, wherein a conjugate acid of the base has a pKa between        6, 7, 8, 9, or 10 and 11, e.g., between about 6, 7, 8, or 9 and        10, e.g., between about 7 and 9, e.g., between about 8 and 9, is        at least 1:2, e.g., at least about 1:2, 1:3, 1:4, or 1:5 to 1:6,        1:7, 1:8 to 1:10, 1:15, 1:20, or 1:30, e.g., at least about        1:2.5 to 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:30,        e.g., at least about 1:2.5, e.g., at least about 1:5, e.g. at        least about 1:10.    -   1.120 Kit 1.71-1.119 wherein the solvent, e.g., the sterile        solution, comprises one or more bulking agents, e.g., one or        more of maltose, mannose, ribose, cyclodextrin, mannitol,        lactose, sucrose, trehalose, sorbitol, glucose, raffinose,        arginine, glycine, histidine, dextran (e.g., dextran 40),        polyvinylpyrrolidone, polyethylene glycol, and polypropylene        glycol, e.g., one or more of mannitol, glucose, sucrose,        lactose, trehalose, and dextran (e.g., dextran 40).    -   1.121 Kit 1.71-1.120 wherein the solvent, e.g., the sterile        solution, comprises 5 or 10 or 50 mg to 2 or 5 g of one or more        bulking agents, e.g., from about 50 or 100 mg to 200, 300, 500,        or 800 mg, or 1, 1.5, 2, 3, 4, or 5 g of one or more bulking        agents.    -   1.122 Kit 1.71-1.121 wherein the solvent, e.g., the sterile        solution, comprises dextran (e.g., dextran 40).    -   1.123 Kit 1.122 wherein the solvent, e.g. the sterile solution,        comprises 5 or 10 or 50 mg to 2 or 5 g dextran (e.g., dextran        40), e.g., from about 50 or 100 mg to 200, 300, 500, or 800 mg,        or 1, 1.5, 2, 3, 4, or 5 g dextran (e.g., dextran 40).    -   1.124 Kit 1.71-1.123 wherein the solvent, e.g., the sterile        solution, comprises one or more solubilizing agents, e.g.,        ethylenediamine tetraacetic acid (EDTA) or a salt thereof (e.g.,        calcium disodium EDTA, disodium EDTA, sodium EDTA), alpha        cyclodextrin, hydroxypropyl-β-cyclodextrin, polysorbate 80,        tert-butanol, isopropanol, dichloromethane, ethanol, acetone,        and glycerol; one or more collapse temperature modifiers which        may shift the overall collapse temperature higher, e.g., one or        more of dextran, Ficoll®, gelatin, and hydroxyethyl starch; one        or more tonicity modifiers, e.g., one or more of sodium        chloride, potassium chloride, sucrose, mannitol, and glucose;        and one or more antimicrobial agents, e.g., one or more of        benzyl alcohol, phenol, 2-phenoxyethanol, m-cresol,        chlorobutanol, parabens (e.g., methyl paraben, ethyl paraben,        propyl paraben), benzalkonium chloride, benzethonium chloride,        myristyl gamma-picolinium salt (e.g., myristyl gamma-picolinium        chloride), and organomercury compounds and salts (e.g., phenyl        mercuric acetate, phenyl mercuric borate, phenyl mercuric        nitrate, and thimerosal).    -   1.125 Kit 1.71-1.124 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is admixed with the solvent, e.g., an        aqueous solution, to form a solution wherein the pH is between        pH 7 and pH 10.5, e.g., between pH 7 and pH 9.5, e.g., between        pH 7 and pH 8.    -   1.126 Kit 1.71-1.125 wherein the solution is filtered to remove        particles and microbes, e.g., filtered prior to injection.    -   1.127 Kit 1.71-1.126 wherein the solution is administered about        24 hours, 12 hours, 10 hours, 8 hours, 2 hours, 1 hour, 30        minutes, 20 minutes, 15 minutes, 10 minutes, 5 minutes, 3        minutes, 2 minutes or 1 minute or less after admixture.    -   1.128 Kit I or 1.1-1.127 wherein the kit comprises one or more        additional therapeutic agents, e.g., one or more additional        therapeutic agents for cerebral edema, stroke, traumatic brain        injury, glioma (e.g., glioblastoma), meningitis, acute mountain        sickness, infection, metabolic disorder, hypoxia, water        intoxication, hepatic failure, hepatic encephalopathy, diabetic        ketoacidosis, abscess, eclampsia, Creutzfeldt-Jakob disease,        lupus cerebritis, optic nerve edema, hyponatremia, fluid        retention, ovarian hyperstimulation syndrome, epilepsy, retinal        ischemia or other diseases of the eye associated with        abnormalities in intraocular pressure and/or tissue hydration,        myocardial ischemia, myocardial ischemia/reperfusion injury,        myocardial infarction, myocardial hypoxia, congestive heart        failure, sepsis, neuromyelitis optica, or migraines.    -   1.129 Kit I or 1.1-1.128 wherein the kit comprises one or more        additional therapeutic agents, e.g., one or more additional        therapeutic agents for pulmonary edema, fibromyalgia, or        multiple sclerosis.    -   1.130 Kit I or 1.1-1.129 wherein the kit comprises instructions        for using        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to treat or control a disease or condition        mediated by an aquaporin, e.g., diseases or conditions of water        imbalance and other diseases, for example, edema of the brain or        spinal cord, e.g., cerebral edema, e.g. cerebral edema        consequent to head trauma, ischemic stroke, glioma, meningitis,        acute mountain sickness, epileptic seizure, infection, metabolic        disorder, hypoxia (including general systemic hypoxia and        hypoxia due to cardiac arrest), water intoxication, hepatic        failure, hepatic encephalopathy, diabetic ketoacidosis, abscess,        eclampsia, Creutzfeldt-Jakob disease, lupus cerebritis, cardiac        arrest, microgravity and/or radiation exposure, or an invasive        central nervous system procedure, e.g., neurosurgery,        endovascular clot removal, spinal tap, aneurysm repair, or deep        brain stimulation or, e.g., spinal cord edema consequent to        spinal cord trauma, e.g., spinal cord compression; or optic        nerve edema, e.g., optic nerve edema consequent to microgravity        and/or radiation exposure; or retinal edema; or hyponatremia or        excessive fluid retention, e.g., consequent to heart failure        (HF), liver cirrhosis, nephrotic disorder, syndrome of        inappropriate antidiuretic hormone secretion (SIADH), or        infertility treatment; or ovarian hyperstimulation syndrome; or        epilepsy, retinal ischemia or other diseases of the eye        associated with abnormalities in intraocular pressure and/or        tissue hydration, myocardial ischemia, myocardial        ischemia/reperfusion injury, myocardial infarction, myocardial        hypoxia, congestive heart failure, sepsis, neuromyelitis optica,        or glioblastoma; or migraines.    -   1.131 Kit 1 or 1.1-1.130 wherein the kit comprises instructions        for using        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to treat or control a disease or condition        mediated by an aquaporin, e.g., diseases or conditions of water        imbalance and other diseases, for example, pulmonary edema,        fibromyalgia, or multiple sclerosis.    -   1.132 Kit I or 1.1-1.131 wherein the kit comprises instructions        for administering        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate to a patient in need thereof.    -   1.133 Kit I or 1.1-1.132 wherein the kit comprises instructions        for mixing        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate and one or more pharmaceutically acceptable        excipients.    -   1.134 Kit I wherein the kit comprises a pharmaceutical        composition comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate, e.g., Composition I, e.g., a composition        of 1.1-1.73.    -   1.135 Kit 1.134 wherein the kit comprises instructions for using        the pharmaceutical composition to treat or control a disease or        condition mediated by an aquaporin, e.g., diseases or conditions        of water imbalance and other diseases, for example, edema of the        brain or spinal cord, e.g., cerebral edema, e.g. cerebral edema        consequent to head trauma, ischemic stroke, glioma, meningitis,        acute mountain sickness, epileptic seizure, infection, metabolic        disorder, hypoxia (including general systemic hypoxia and        hypoxia due to cardiac arrest), water intoxication, hepatic        failure, hepatic encephalopathy, diabetic ketoacidosis, abscess,        eclampsia, Creutzfeldt-Jakob disease, lupus cerebritis, cardiac        arrest, microgravity and/or radiation exposure, or an invasive        central nervous system procedure, e.g., neurosurgery,        endovascular clot removal, spinal tap, aneurysm repair, or deep        brain stimulation or, e.g., spinal cord edema consequent to        spinal cord trauma, e.g., spinal cord compression; or optic        nerve edema, e.g., optic nerve edema consequent to microgravity        and/or radiation exposure; or retinal edema; or hyponatremia or        excessive fluid retention, e.g., consequent to heart failure        (HF), liver cirrhosis, nephrotic disorder, syndrome of        inappropriate antidiuretic hormone secretion (SIADH), or        infertility treatment; ovarian hyperstimulation syndrome; or        epilepsy, retinal ischemia or other diseases of the eye        associated with abnormalities in intraocular pressure and/or        tissue hydration, myocardial ischemia, myocardial        ischemia/reperfusion injury, myocardial infarction, myocardial        hypoxia, congestive heart failure, sepsis, neuromyelitis optica,        or glioblastoma; or migraines.    -   1.136 Kit 1.134 wherein the kit comprises instructions for using        the pharmaceutical composition to treat or control a disease or        condition mediated by an aquaporin, e.g., diseases or conditions        of water imbalance and other diseases, for example, pulmonary        edema, fibromyalgia, or multiple sclerosis.    -   1.137 Kit 1.134 wherein the kit comprises instructions for        administering the pharmaceutical composition to a patient in        need thereof.    -   1.138 Kit 1.134 wherein the kit comprises instructions for        preparing the pharmaceutical composition.    -   1.139 Kit I or 1.1-1.138 wherein the kit is for use in any of        the methods described herein, e.g., for use in Method A, e.g.,        Method A.1-A.58, for use in Method B, e.g., Method B.1-B.41,        e.g., for use in Method C, e.g., C.1-C.8, e.g., for use in        Method D, e.g., D.1-D.19, e.g., for use in Method E, e.g.,        E.1-E.59, e.g., for use in Method F, e.g., F.1-F.5, e.g., for        use in Method G, e.g., G.1-G.58, e.g., for use in Method H,        e.g., H.1-H.9, vida infra.

In some embodiments, the kit is prepared by transferring a liquidcomprising 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyldihydrogen phosphate to a container, e.g., a vial, in a predeterminedvolume first and then subjecting the liquid to a lyophilization process.Alternatively, liquid can be lyophilized in a large volume and then apredetermined amount of the lyophilized preparation can be placed in acontainer.

In yet another embodiment, provided is a method (Method A) of treatingor controlling a disease or condition mediated by an aquaporincomprising administering to a patient in need thereof a pharmaceuticalcomposition comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate, e.g., Composition I, e.g., composition 1.1-1.124.

Further provided is Method A as follows:

-   -   A.1 Method A wherein the aquaporin is AQP4.    -   A.2 Method A or A.1 wherein the condition to be treated or        controlled is edema, e.g. edema of the brain or spinal cord,        e.g., cerebral edema, e.g. cerebral edema consequent to head        trauma, ischemic stroke, glioma, meningitis, acute mountain        sickness, epileptic seizure, infection, metabolic disorder,        water intoxication, hepatic failure, hepatic encephalopathy, or        diabetic ketoacidosis or, e.g., spinal cord edema, e.g., spinal        cord edema consequent to spinal cord trauma, e.g., spinal cord        compression.    -   A.3 Method A, A.1, or A.2 further comprising a treatment        selected from one or more of the following: optimal head and        neck positioning to facilitate venous outflow, e.g. head        elevation 300; avoidance of dehydration; systemic hypotension;        maintenance of normothermia or hypothermia; aggressive measures;        osmotherapy, e.g., using mannitol or hypertonic saline;        hyperventilation; therapeutic pressor therapy to enhance        cerebral perfusion; administration of barbiturates to reduce        cerebral metabolism (CMO₂); hemicraniectomy; administration of        aspirin; administration of amantadine; intravenous thrombolysis        (e.g. using rtPA); mechanical clot removal; angioplasty; and/or        stents.    -   A.4 Method A.2 wherein the patient is at elevated risk of        cerebral edema, e.g., due to head trauma, ischemic stroke,        glioma, meningitis, acute mountain sickness, epileptic seizure,        infection, metabolic disorder, water intoxication, hepatic        failure, hepatic encephalopathy, or diabetic ketoacidosis.    -   A.5 Method A.2 wherein the patient has suffered a stroke, head        injury, or spinal injury.    -   A.6 Method A.5 wherein the patient has suffered a stroke, head        injury or spinal injury within 12 hours, e.g. within 6 hours,        preferably within 3 hours of commencing treatment.    -   A.7 Method A.2 wherein the patient is at elevated risk of        suffering a stroke, head injury or spinal injury, e.g., in        combat or in an athletic competition.    -   A.8 Method A or A.1-A.7 wherein the patient already has cerebral        edema.    -   A.9 Method A or A.1-A.8 wherein the condition to be treated or        controlled is cerebral edema consequent to a stroke or a        traumatic brain injury.    -   A.10 Method A or A.1-A.9 wherein the condition to be treated or        controlled is cerebral edema consequent to a middle cerebral        artery stroke.    -   A.11 Method A or A.1-A.9 wherein the condition to be treated or        controlled is cerebral edema consequent to closed head trauma.    -   A.12 Method A or A.1-A.4 wherein the condition to be treated or        controlled is cerebral edema consequent to an epileptic seizure.    -   A.13 Method A or A.1-A.4 wherein the condition to be treated or        controlled is cerebral edema consequent to an infection.    -   A.14 Method A or A.1-A.4 wherein the condition to be treated or        controlled is cerebral edema consequent to a metabolic disorder.    -   A.15 Method A or A.1-A.4 wherein the condition to be treated or        controlled is cerebral edema consequent to glioma.    -   A.16 Method A or A.1-A.4 wherein the condition to be treated or        controlled is cerebral edema consequent to meningitis.    -   A.17 Method A or A.1-A.4 wherein the condition to be treated or        controlled is cerebral edema consequent to acute mountain        sickness.    -   A.18 Method A or A.1-A.4 wherein the condition to be treated or        controlled is cerebral edema consequent to water intoxication.    -   A.19 Method A or A.1-A.4 wherein the condition to be treated or        controlled is cerebral edema consequent to hepatic failure,        hepatic encephalopathy, or diabetic ketoacidosis.    -   A.20 Method A or A.1-A.3 wherein the condition to be treated or        controlled is cerebral edema consequent to an abscess.    -   A.21 Method A or A.1-A.3 wherein the condition to be treated or        controlled is cerebral edema consequent to eclampsia.    -   A.22 Method A or A.1-A.3 wherein the condition to be treated or        controlled is cerebral edema consequent to Creutzfeldt-Jakob        disease.    -   A.23 Method A or A.1-A.3 wherein the condition to be treated or        controlled is cerebral edema consequent to lupus cerebritis.    -   A.24 Method A or A.1-A.3 wherein the condition to be treated or        controlled is edema consequent to hypoxia, e.g., general        systemic hypoxia, e.g., hypoxia caused by an interruption of        blood perfusion, for example wherein the edema is cerebral edema        consequent to hypoxia caused by cardiac arrest, stroke, or other        interruption of blood perfusion to the brain, or wherein the        edema is cardiac edema consequent to cardiac ischemia or other        interruption of blood flow to the heart.    -   A.25 Method A or A.1-A.3 wherein the condition to be treated or        controlled is cerebral edema consequent to microgravity and/or        radiation exposure, e.g., exposure from space flight or from        working with radioactive materials or from working in        radioactive areas.    -   A.26 Method A or A.1-A.3 wherein the condition to be treated or        controlled is cerebral edema consequent to an invasive central        nervous system procedure, e.g., neurosurgery, endovascular clot        removal, spinal tap, aneurysm repair, or deep brain stimulation.    -   A.27 Method A.25 or A.26 wherein the patient is at elevated risk        of edema, e.g., due to microgravity and/or radiation exposure,        neurosurgery, endovascular clot removal, spinal tap, aneurysm        repair, or deep brain stimulation.    -   A.28 Method A.25 or A.26 wherein the patient already has edema.    -   A.29 Method A or A.1-A.28 wherein the edema is cytotoxic        cerebral edema or is primarily cytotoxic cerebral edema.    -   A.30 Method A, A.1-A.19, or A.24 wherein the edema is cytotoxic        cerebral edema or is primarily cytotoxic cerebral edema.    -   A.31 Method A, A.1, or A.2 wherein the condition to be treated        or controlled is spinal cord edema, e.g., spinal cord edema        consequent to a spinal cord trauma, e.g., spinal cord        compression.    -   A.32 Method A.31 wherein the condition to be treated or        controlled is spinal cord edema consequent to spinal cord        compression.    -   A.33 Method A, A.1, or A.2 wherein the condition to be treated        or controlled is optic nerve edema, e.g., optic nerve edema        consequent to microgravity and/or radiation exposure, e.g.,        exposure from space flight or from working with radioactive        materials or from working in radioactive areas.    -   A.34 Method A, A.1, or A.2 wherein the condition to be treated        or controlled is retinal edema.    -   A.35 Method A, A.1, or A.2 wherein the condition to be treated        or controlled is pulmonary edema.    -   A.36 Method A or A.1 wherein the condition to be treated or        controlled is epilepsy.    -   A.37 Method A or A.1 wherein the condition to be treated or        controlled is retinal ischemia or other diseases of the eye        associated with abnormalities in intraocular pressure and/or        tissue hydration.    -   A.38 Method A or A.1 wherein the condition to be treated or        controlled is myocardial ischemia.    -   A.39 Method A or A.1, wherein the condition to be treated or        controlled is myocardial ischemia/reperfusion injury.    -   A.40 Method A or A.1 wherein the condition to be treated or        controlled is myocardial infarction.    -   A.41 Method A or A.1 wherein the condition to be treated or        controlled is myocardial hypoxia.    -   A.42 Method A or A.1 wherein the condition to be treated or        controlled is congestive heart failure.    -   A.43 Method A or A.1 wherein the condition to be treated or        controlled is sepsis.    -   A.44 Method A or A.1 wherein the condition to be treated or        controlled is a migraine.    -   A.45 Method A or A.1 wherein the condition to be treated or        controlled is neuromyelitis optica.    -   A.46 Method A or A.1 wherein the condition to be treated or        controlled is glioblastoma.    -   A.47 Method A or A.1 wherein the condition to be treated or        controlled is fibromyalgia.    -   A.48 Method A or A.1 wherein the condition to be treated or        controlled is multiple sclerosis.    -   A.49 Method A wherein the aquaporin is AQP2.    -   A.50 Method A or A.49 wherein the condition to be treated or        controlled is hyponatremia or excessive fluid retention, e.g.,        consequent to heart failure (HF), for example congestive heart        failure, liver cirrhosis, nephrotic disorder, syndrome of        inappropriate antidiuretic hormone secretion (SIADH), or        infertility treatment.    -   A.51 Method A, A.49, or A.50 wherein the condition to be treated        or controlled is ovarian hyperstimulation syndrome.    -   A.52 Method A, A.49, or A.50 further comprising one or more of        restriction of dietary sodium, fluid and/or alcohol; and/or        administration of one or more diuretics, vasopressin receptor        antagonists, angiotensin converting enzyme (ACE) inhibitors,        aldosterone inhibitors, angiotensin receptor blockers (ARBs),        beta-adrenergic antagonists (beta-blockers), and/or digoxin.    -   A.53 Method A or A.1-A.42 wherein the pharmaceutical composition        is administered orally.    -   A.54 Method A or A.1-A.52 wherein the pharmaceutical composition        is administered parenterally.    -   A.55 Method A.54 wherein the pharmaceutical composition is        administered by injection, e.g., subcutaneously,        intramuscularly, intravenously, or intrathecally, e.g., a bolus        injected subcutaneously, intramuscularly, intravenously, or        intrathecally.    -   A.56 Method A.55 wherein the pharmaceutical composition is        administered intravenously, e.g., IV bolus and/or IV infusion,        e.g., IV bolus followed by IV infusion.    -   A.57 Method A or A.1-A.56 wherein the patient is human.    -   A.58 Method A or A.1-A.57 wherein the onset of action after        administration of the pharmaceutical composition is fairly        rapid.

In yet another embodiment, provided is a method (Method B) of treatingor controlling edema, e.g. edema of the brain or spinal cord, e.g.,cerebral edema, e.g. cerebral edema consequent to head trauma, ischemicstroke, glioma, meningitis, acute mountain sickness, epileptic seizure,infection, metabolic disorder, hypoxia, water intoxication, hepaticfailure, hepatic encephalopathy, diabetic ketoacidosis, abscess,eclampsia, Creutzfeldt-Jakob disease, lupus cerebritis, cardiac arrest,microgravity and/or radiation exposure, or invasive central nervoussystem procedures, e.g., neurosurgery, endovascular clot removal, spinaltap, aneurysm repair, or deep brain stimulation or, e.g., optic nerveedema, e.g., optic nerve edema consequent to microgravity and/orradiation exposure or, e.g., retinal edema or, e.g., spinal cord edema,e.g., spinal cord edema consequent to spinal cord trauma, e.g., spinalcord compression, or e.g., pulmonary edema, comprising administering apharmaceutical composition comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate, e.g., Composition I, e.g., composition 1.1-1.124, to apatient in need thereof.

Further provided is Method B as follows:

-   -   B.1 Method B further comprising a treatment selected from one or        more of the following: optimal head and neck positioning to        facilitate venous outflow, e.g. head elevation 30°; avoidance of        dehydration; systemic hypotension; maintenance of normothermia        or hypothermia; aggressive measures; osmotherapy, e.g., using        mannitol or hypertonic saline; hyperventilation; therapeutic        pressor therapy to enhance cerebral perfusion; administration of        barbiturates to reduce cerebral metabolism (CMO₂);        hemicraniectomy; administration of aspirin; administration of        amantadine; intravenous thrombolysis (e.g. using rtPA);        mechanical clot removal; angioplasty; and/or stents.    -   B.2 Method B wherein the patient is at elevated risk of cerebral        edema, e.g., due to head trauma, ischemic stroke, glioma,        meningitis, acute mountain sickness, epileptic seizure,        infection, metabolic disorder, water intoxication, hepatic        failure, hepatic encephalopathy, or diabetic ketoacidosis.    -   B.3 Method B wherein the patient has suffered a stroke, head        injury, or spinal injury.    -   B.4 Method B.3 wherein the patient has suffered a stroke, head        injury or spinal injury within 12 hours, e.g. within 6 hours,        preferably within 3 hours of commencing treatment.    -   B.5 Method B wherein the patient is at elevated risk of        suffering a stroke, head injury or spinal injury, e.g., in        combat or in an athletic competition.    -   B.6 Method B or B.1-B.5 wherein the patient already has cerebral        edema.    -   B.7 Method B or B.1-B.6 wherein the condition to be treated or        controlled is cerebral edema consequent to a stroke or a        traumatic brain injury.    -   B.8 Method B or B.1-B.7 wherein the condition to be treated or        controlled is cerebral edema consequent to a middle cerebral        artery stroke.    -   B.9 Method B or B.1-B.7 wherein the condition to be treated or        controlled is cerebral edema consequent to a closed head trauma.    -   B.10 Method B, B.1, or B.2 wherein the condition to be treated        or controlled is cerebral edema consequent to an epileptic        seizure.    -   B.11 Method B, B.1, or B.2 wherein the condition to be treated        or controlled is cerebral edema consequent to an infection.    -   B.12 Method B, B.1, or B.2 wherein the condition to be treated        or controlled is cerebral edema consequent to a metabolic        disorder.    -   B.13 Method B, B.1, or B.2 wherein the condition to be treated        or controlled is cerebral edema consequent to glioma.    -   B.14 Method B, B.1, or B.2 wherein the condition to be treated        or controlled is cerebral edema consequent to meningitis.    -   B.15 Method B, B.1, or B.2 wherein the condition to be treated        or controlled is cerebral edema consequent to acute mountain        sickness.    -   B.16 Method B, B.1, or B.2 wherein the condition to be treated        or controlled is cerebral edema consequent to water        intoxication.    -   B.17 Method B, B.1, or B.2 wherein the condition to be treated        or controlled is cerebral edema consequent to hepatic failure,        hepatic encephalopathy, or diabetic ketoacidosis.    -   B.18 Method B or B.1 wherein the condition to be treated or        controlled is cerebral edema consequent to an abscess.    -   B.19 Method B or B.1 wherein the condition to be treated or        controlled is cerebral edema consequent to eclampsia.    -   B.20 Method B or B.1 wherein the condition to be treated or        controlled is cerebral edema consequent to Creutzfeldt-Jakob        disease.    -   B.21 Method B or B.1 wherein the condition to be treated or        controlled is cerebral edema consequent to lupus cerebritis.    -   B.22 Method B or B.1 wherein the condition to be treated or        controlled is edema consequent to hypoxia, e.g., general        systemic hypoxia, e.g., hypoxia caused by an interruption of        blood perfusion, for example wherein the edema is cerebral edema        consequent to hypoxia caused by cardiac arrest, stroke, or other        interruption of blood perfusion to the brain, or wherein the        edema is cardiac edema consequent to cardiac ischemia or other        interruption of blood flow to the heart.    -   B.23 Method B or B.1 wherein the condition to be treated or        controlled is cerebral edema consequent to microgravity        exposure, e.g., exposure from space flight or from working with        radioactive materials or from working in radioactive areas.    -   B.24 Method B or B.1 wherein the condition to be treated or        controlled is cerebral edema consequent to invasive central        nervous system procedures, e.g., neurosurgery, endovascular clot        removal, spinal tap, aneurysm repair, or deep brain stimulation.    -   B.25 Method B.23 or B.24 wherein the patient is at elevated risk        of edema, e.g., due to microgravity and/or radiation exposure,        neurosurgery, endovascular clot removal, spinal tap, aneurysm        repair, or deep brain stimulation.    -   B.26 Method B.23 or B.24 wherein the patient already has edema.    -   B.27 Method B or B.1-B.26 wherein the edema is cytotoxic        cerebral edema or is primarily cytotoxic cerebral edema.    -   B.28 Method B, B.1-B.17, or B.22 wherein the edema is cytotoxic        cerebral edema or is primarily cytotoxic cerebral edema.    -   B.29 Method B wherein the condition to be treated or controlled        is spinal cord edema, e.g., spinal cord edema consequent to        spinal cord trauma, e.g., spinal cord compression.    -   B.30 Method B.29 wherein the condition to be treated or        controlled is spinal cord edema consequent to spinal cord        compression.    -   B.31 Method B wherein the condition to be treated or controlled        is optic nerve edema, e.g., optic nerve edema consequent to        microgravity and/or radiation exposure, e.g., exposure from        space flight or from working with radioactive materials or from        working in radioactive areas.    -   B.32 Method B wherein the condition to be treated or controlled        is retinal edema.    -   B.33 Method B wherein the condition to be treated or controlled        is pulmonary edema.    -   B.34 Method B or B.1-B.33 wherein the duration of treatment with        the pharmaceutical composition is less than 21 days, e.g., less        than 2 weeks, e.g., one week or less.    -   B.35 Method B or B.1-B.34 wherein the pharmaceutical composition        is administered orally.    -   B.36 Method B or B.1-B.34 wherein the pharmaceutical composition        is administered parenterally.    -   B.37 Method B.36 wherein the pharmaceutical composition is        administered by injection, e.g., subcutaneously,        intramuscularly, intravenously, or intrathecally, e.g., a bolus        administered subcutaneously, intramuscularly, intravenously, or        intrathecally.    -   B.38 Method B.37 wherein the pharmaceutical composition is        administered intravenously, e.g., IV bolus and/or IV infusion,        e.g., IV bolus followed by IV infusion.    -   B.39 Method B or B.1-B.38 wherein the patient is human.    -   B.40 Method B or B.1-B.39 wherein the onset of action after        administration of the pharmaceutical composition is fairly        rapid.    -   B.41 Method B or B.1-B.40 wherein the        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate binds to AQP4.

In yet another embodiment, provided is a method (Method C) of treatingor controlling a condition selected from hyponatremia and excessivefluid retention, e.g., consequent to heart failure (HF), for examplecongestive heart failure, liver cirrhosis, nephrotic disorder, syndromeof inappropriate antidiuretic hormone secretion (SIADH), or infertilitytreatment, comprising administering a pharmaceutical compositioncomprising 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyldihydrogen phosphate, e.g., Composition I, e.g., composition 1.1-1.124,to a patient in need thereof.

Further provided is Method C as follows:

-   -   C.1 Method C further comprising one or more of restriction of        dietary sodium, fluid and/or alcohol; and/or administration of        one or more diuretics, vasopressin receptor antagonists,        angiotensin converting enzyme (ACE) inhibitors, aldosterone        inhibitors, angiotensin receptor blockers (ARBs),        beta-adrenergic antagonists (beta-blockers), and/or digoxin.    -   C.2 Method C or C.1 wherein the pharmaceutical composition is        administered orally.    -   C.3 Method C or C.1 wherein the pharmaceutical composition is        administered parenterally.    -   C.4 Method C.3 wherein the pharmaceutical composition is        administered by injection, e.g., subcutaneously,        intramuscularly, intravenously, or intrathecally, e.g., a bolus        injected subcutaneously, intramuscularly, intravenously, or        intrathecally.    -   C.5 Method C.4 wherein the pharmaceutical composition is        administered intravenously, e.g., IV bolus and/or IV infusion,        e.g., IV bolus followed by IV infusion.    -   C.6 Method C or C.1-C.5 wherein the patient is human.    -   C.7 Method C or C.1-C.6 wherein the onset of action after        administration of the pharmaceutical composition is fairly        rapid.    -   C.8 Method C or C.1-C.7 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate binds to AQP2.

In yet another embodiment, provided is a method (Method D) of treatingor controlling a condition selected from epilepsy, retinal ischemia orother diseases of the eye associated with abnormalities in intraocularpressure and/or tissue hydration, myocardial ischemia, myocardialischemia/reperfusion injury, myocardial infarction, myocardial hypoxia,congestive heart failure, sepsis, neuromyelitis optica, glioblastoma,fibromyalgia, multiple sclerosis, and a migraine comprisingadministering a pharmaceutical composition comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate, e.g., Composition I, e.g., composition 1.1-1.124, to apatient in need thereof.

Further provided is Method D as follows:

-   -   D.1 Method D wherein the condition to be treated or controlled        is retinal ischemia or other diseases of the eye associated with        abnormalities in intraocular pressure and/or tissue hydration.    -   D.2 Method D wherein the condition to be treated or controlled        is myocardial ischemia.    -   D.3 Method D wherein the condition to be treated or controlled        is myocardial ischemia/reperfusion injury.    -   D.4 Method D wherein the condition to be treated or controlled        is myocardial infarction.    -   D.5 Method D wherein the condition to be treated or controlled        is myocardial hypoxia.    -   D.6 Method D wherein the condition to be treated or controlled        is congestive heart failure.    -   D.7 Method D wherein the condition to be treated or controlled        is sepsis.    -   D.8 Method D wherein the condition to be treated or controlled        is neuromyelitis optica.    -   D.9 Method D wherein the condition to be treated or controlled        is glioblastoma.    -   D.10 Method D wherein the condition to be treated or controlled        is fibromyalgia.    -   D.11 Method D wherein the condition to be treated or controlled        is multiple sclerosis.    -   D. 12 Method D wherein the condition to be treated or controlled        is a migraine.    -   D.13 Method D or D.1-D.12 wherein the pharmaceutical composition        comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered orally.    -   D.14 Method D or D.1-D.12 wherein the pharmaceutical composition        comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered parenterally.    -   D.15 Method D.14 wherein the pharmaceutical composition        comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered by injection, e.g.,        subcutaneously, intramuscularly, intravenously, or        intrathecally, e.g., a bolus injected subcutaneously,        intramuscularly, intravenously, or intrathecally.    -   D.16 Method D.15 wherein the pharmaceutical composition        comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered intravenously, e.g., IV        bolus and/or IV infusion, e.g., IV bolus followed by IV        infusion.    -   D.17 Method D or D.1-D.16 wherein the patient is human.    -   D.18 Method D or D.1-D.17 wherein the onset of action after        administration of the pharmaceutical composition comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is fairly rapid.    -   D.19 Method D or D.1-D.18 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate binds to AQP4.

In yet another embodiment, provided is a method (Method E) of treatingor controlling a disease or condition mediated by an aquaporincomprising administering to a patient in need thereof a pharmaceuticalcomposition comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate, e.g., Composition I, e.g., composition 1.1-1.124, in anamount effective to inhibit the aquaporin, for example

Further provided is Method E as follows:

-   -   E.1 Method E wherein the aquaporin is AQP4.    -   E.2 Method E or E.1 wherein the condition to be treated or        controlled is selected from edema, e.g. edema of the brain or        spinal cord, e.g., cerebral edema, e.g. cerebral edema        consequent to head trauma, ischemic stroke, glioma, meningitis,        acute mountain sickness, epileptic seizure, infection, metabolic        disorder, water intoxication, hepatic failure, hepatic        encephalopathy, or diabetic ketoacidosis or, e.g., spinal cord        edema, e.g., spinal cord edema consequent to spinal cord trauma,        e.g., spinal cord compression.    -   E.3 Method E, E.1, or E.2 further comprising a treatment        selected from one or more of the following: optimal head and        neck positioning to facilitate venous outflow, e.g. head        elevation 300; avoidance of dehydration; systemic hypotension;        maintenance of normothermia or hypothermia; aggressive measures;        osmotherapy, e.g., using mannitol or hypertonic saline;        hyperventilation; therapeutic pressor therapy to enhance        cerebral perfusion; administration of barbiturates to reduce of        cerebral metabolism (CMO₂); hemicraniectomy; administration of        aspirin; administration of amantadine; intravenous thrombolysis        (e.g. using rtPA); mechanical clot removal; angioplasty; and/or        stents.    -   E.4 Method E.2 wherein the patient is at elevated risk of        cerebral edema, e.g., due to head trauma, ischemic stroke,        glioma, meningitis, acute mountain sickness, epileptic seizure,        infection, metabolic disorder, water intoxication, hepatic        failure, hepatic encephalopathy, or diabetic ketoacidosis.    -   E.5 Method E.2 wherein the patient has suffered a stroke, head        injury, or spinal injury.    -   E.6 Method E.5 wherein the patient has suffered a stroke, head        injury or spinal injury within 12 hours, e.g. within 6 hours,        preferably within 3 hours of commencing treatment.    -   E.7 Method E.2 wherein the patient is at elevated risk of        suffering a stroke, head injury or spinal injury, e.g., in        combat or in an athletic competition.    -   E.8 Method E or E.1-E.7 wherein the patient already has cerebral        edema.    -   E.9 Method E or E.1-E.8 wherein the condition to be treated or        controlled is cerebral edema consequent to a stroke or a        traumatic brain injury.    -   E.10 Method E or E.1-E.9 wherein the condition to be treated or        controlled is cerebral edema consequent to a middle cerebral        artery stroke.    -   E.11 Method E or E.1-E.9 wherein the condition to be treated or        controlled is cerebral edema consequent to a closed head trauma.    -   E.12 Method E or E.1-E.4 wherein the condition to be treated or        controlled is cerebral edema consequent to an epileptic seizure.    -   E.13 Method E or E.1-E.4 wherein the condition to be treated or        controlled is cerebral edema consequent an infection.    -   E.14 Method E or E.1-E.4 wherein the condition to be treated or        controlled is cerebral edema consequent to a metabolic disorder.    -   E.15 Method E or E.1-E.4 wherein the condition to be treated or        controlled is cerebral edema consequent to glioma.    -   E.16 Method E or E.1-E.4 wherein the condition to be treated or        controlled is cerebral edema consequent to meningitis.    -   E.17 Method E or E.1-E.4 wherein the condition to be treated or        controlled is cerebral edema consequent to acute mountain        sickness.    -   E.18 Method E or E.1-E.4 wherein the condition to be treated or        controlled is cerebral edema consequent to water intoxication.    -   E.19 Method E or E.1-E.4 wherein the condition to be treated or        controlled is cerebral edema consequent to hepatic failure,        hepatic encephalopathy, or diabetic ketoacidosis.    -   E.20 Method E or E.1-E.3 wherein the condition to be treated or        controlled is cerebral edema consequent to an abscess.    -   E.21 Method E or E.1-E.3 wherein the condition to be treated or        controlled is cerebral edema consequent to eclampsia.    -   E.22 Method E or E.1-E.3 wherein the condition to be treated or        controlled is cerebral edema consequent to Creutzfeldt-Jakob        disease.    -   E.23 Method E or E.1-E.3 wherein the condition to be treated or        controlled is cerebral edema consequent to lupus cerebritis.    -   E.24 Method E or E.1-E.3 wherein the condition to be treated or        controlled is edema consequent to hypoxia, e.g., general        systemic hypoxia, e.g., hypoxia caused by an interruption of        blood perfusion, for example wherein the edema is cerebral edema        consequent to hypoxia caused by cardiac arrest, stroke, or other        interruption of blood perfusion to the brain, or wherein the        edema is cardiac edema consequent to cardiac ischemia or other        interruption of blood flow to the heart.    -   E.25 Method E or E.1-E.3 wherein the condition to be treated or        controlled is cerebral edema consequent to microgravity and/or        radiation exposure, e.g., exposure from space flight or from        working with radioactive materials or from working in        radioactive areas.    -   E.26 Method E or E.1-E.3 wherein the condition to be treated or        controlled is cerebral edema consequent to invasive central        nervous system procedures, e.g., neurosurgery, endovascular clot        removal, spinal tap, aneurysm repair, or deep brain stimulation.    -   E.27 Method E.25 or E.26 wherein the patient is at elevated risk        of edema, e.g., due to microgravity and/or radiation exposure,        neurosurgery, endovascular clot removal, spinal tap, aneurysm        repair, or deep brain stimulation.    -   E.28 Method E.25 or E.26 wherein the patient already has edema.    -   E.29 Method E or E.1-E.28 wherein the edema is cytotoxic        cerebral edema or is primarily cytotoxic cerebral edema.    -   E.30 Method E, E.1-E.19, or E.24 wherein the edema is cytotoxic        cerebral edema or is primarily cytotoxic cerebral edema.    -   E.31 Method E, E.1, or E.2 wherein the condition to be treated        or controlled is spinal cord edema, e.g., spinal cord edema        consequent to spinal cord trauma, e.g., spinal cord compression.    -   E.32 Method E.31 wherein the condition to be treated or        controlled is spinal cord edema consequent to spinal cord        compression.    -   E.33 Method E, E.1 or E.2 wherein the condition to be treated or        controlled is optic nerve edema, e.g., optic nerve edema        consequent to microgravity and/or radiation exposure, e.g.,        exposure from space flight or from working with radioactive        materials or from working in radioactive areas.    -   E.34 Method E, E.1, or E.2 wherein the condition to be treated        or controlled is retinal edema.    -   E.35 Method E, E.1, or E.2 wherein the condition to be treated        or controlled is pulmonary edema.    -   E.36 Method E or E.1 wherein the condition to be treated or        controlled is epilepsy.    -   E.37 Method E or E.1 wherein the condition to be treated or        controlled is retinal ischemia or other diseases of the eye        associated with abnormalities in intraocular pressure and/or        tissue hydration.    -   E.38 Method E or E.1 wherein the condition to be treated or        controlled is myocardial ischemia.    -   E.39 Method E or E.1 wherein the condition to be treated or        controlled is myocardial ischemia/reperfusion injury.    -   E.40 Method E or E.1 wherein the condition to be treated or        controlled is myocardial infarction.    -   E.41 Method E or E.1 wherein the condition to be treated or        controlled is myocardial hypoxia.    -   E.42 Method E or E, 1 wherein the condition to be treated or        controlled is congestive heart failure.    -   E.43 Method E or E.1 wherein the condition to be treated or        controlled is sepsis.    -   E.44 Method E or E.1 wherein the condition to be treated or        controlled is a migraine.    -   E.45 Method E or E.1 wherein the condition to be treated or        controlled is neuromyelitis optica.    -   E.46 Method E or E.1 wherein the condition to be treated or        controlled is glioblastoma.    -   E.47 Method E or E.1 wherein the condition to be treated or        controlled is fibromyalgia.    -   E.48 Method E or E.1 wherein the condition to be treated or        controlled is multiple sclerosis.    -   E.49 Method E wherein the aquaporin is AQP2.    -   E.50 Method E or E.49 wherein the condition to be treated is        hyponatremia or excessive fluid retention, e.g., consequent to        heart failure (HF), for example congestive heart failure, liver        cirrhosis, nephrotic disorder, syndrome of inappropriate        antidiuretic hormone secretion (SIADH), or infertility        treatment.    -   E.51 Method E, E.49, or E.50 wherein the condition to be treated        or controlled is ovarian hyperstimulation syndrome.    -   E.52 Method E, E.49, or E.50 further comprising one or more of        restriction of dietary sodium, fluid and/or alcohol; and/or        administration of one or more diuretics, vasopressin receptor        antagonists, angiotensin converting enzyme (ACE) inhibitors,        aldosterone inhibitors, angiotensin receptor blockers (ARBs),        beta-adrenergic antagonists (beta-blockers), and/or digoxin.    -   E.53 Method E or E.1-E.52 wherein the duration of treatment with        the pharmaceutical composition comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is less than 21 days, e.g., less than 2        weeks, e.g., one week or less.    -   E.54 Method E or E.1-E.53 wherein the pharmaceutical composition        comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate e is administered orally.    -   E.55 Method E or E.1-E.53 wherein the pharmaceutical composition        comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered parenterally.    -   E.56 Method E.55 wherein the pharmaceutical composition        comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered by injection, e.g.,        subcutaneously, intramuscularly, intravenously, or        intrathecally, e.g., a bolus injected subcutaneously,        intramuscularly, intravenously, or intrathecally.    -   E.57 Method E.56 wherein the pharmaceutical composition        comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered intravenously, e.g., IV        bolus and/or IV infusion, e.g., IV bolus followed by IV        infusion.    -   E.58 Method E or E.1-E.57 wherein the patient is human.    -   E.59 Method E or E.1-E.58 wherein the onset of action after        administration of the pharmaceutical composition comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is fairly rapid.

In a further embodiment, provided is a method (Method F) of inhibitingan aquaporin in vivo comprising administering a pharmaceuticalcomposition comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate, e.g., Composition I, e.g., composition 1.1-1.124, in anamount effective to inhibit the aquaporin.

Further provided is Method F as follows:

-   -   F.1 Method F wherein the aquaporin is AQP4.    -   F.2 Method F wherein the aquaporin is AQP2.    -   F.3 Method F, F.1, or F.2 wherein the pharmaceutical composition        is administered orally.    -   F.4 Method F, F.1, or F.2 wherein the pharmaceutical composition        is administered parenterally.    -   F.5 Method of F.4 wherein the pharmaceutical composition is        administered intravenously, e.g., IV bolus and/or IV infusion,        e.g., IV bolus followed by IV infusion.

In a further embodiment, provided is a method (Method G) to inhibit anaquaporin in a patient suffering from a disease or condition mediated byan aquaporin comprising administering an effective amount of apharmaceutical composition comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate, e.g., Composition 1, e.g., composition 1.1-1.124, to inhibitthe aquaporin.

Further provided is Method G as follows:

-   -   G.1 Method G wherein the aquaporin is AQP4.    -   G.2 Method G or G.1 wherein the condition to be treated or        controlled is edema, e.g. edema of the brain or spinal cord,        e.g., cerebral edema, e.g. cerebral edema consequent to head        trauma, ischemic stroke, glioma, meningitis, acute mountain        sickness, epileptic seizure, infection, metabolic disorder,        water intoxication, hepatic failure, hepatic encephalopathy, or        diabetic ketoacidosis or, e.g., spinal cord edema, e.g., spinal        cord edema consequent to spinal cord trauma, e.g., spinal cord        compression.    -   G.3 Method G, G.1, or G.2 further comprising a treatment        selected from one or more of the following: optimal head and        neck positioning to facilitate venous outflow, e.g. head        elevation 30°; avoidance of dehydration; systemic hypotension;        maintenance of normothermia or hypothermia; aggressive measures;        osmotherapy, e.g., using mannitol or hypertonic saline;        hyperventilation; therapeutic pressor therapy to enhance        cerebral perfusion; administration of barbiturates to reduce        cerebral metabolism (CMO₂); hemicraniectomy; administration of        aspirin; administration of amantadine; intravenous thrombolysis        (e.g. using rtPA); mechanical clot removal; angioplasty; and/or        stents.    -   G.4 Method G.2 wherein the patient is at elevated risk of        cerebral edema, e.g., due to head trauma, ischemic stroke,        glioma, meningitis, acute mountain sickness, epileptic seizure,        infection, metabolic disorder, water intoxication, hepatic        failure, hepatic encephalopathy, or diabetic ketoacidosis.    -   G.5 Method G.2 wherein the patient has suffered a stroke, head        injury, or spinal injury.    -   G.6 Method G.5 wherein the patient has suffered a stroke, head        injury or spinal injury within 12 hours, e.g. within 6 hours,        preferably within 3 hours of commencing treatment.    -   G.7 Method G.2 wherein the patient is at elevated risk of        suffering a stroke, head injury or spinal injury, e.g., in        combat or in an athletic competition.    -   G.8 Method G or G.1-G.7 wherein the patient already has cerebral        edema.    -   G.9 Method G or G.1-G.8 wherein the condition to be treated or        controlled is cerebral edema consequent to a stroke or a        traumatic brain injury.    -   G.10 Method G or G.1-G.9 wherein the condition to be treated or        controlled is cerebral edema consequent to a middle cerebral        artery stroke.    -   G.11 Method G or G.1-G.9 wherein the condition to be treated or        controlled is cerebral edema consequent to closed head trauma.    -   G.12 Method G or G.1-G.4 wherein the condition to be treated or        controlled is cerebral edema consequent to an epileptic seizure.    -   G.13 Method G or G.1-G.4 wherein the condition to be treated or        controlled is cerebral edema consequent to an infection.    -   G.14 Method G or G.1-G.4 wherein the condition to be treated or        controlled is cerebral edema consequent to a metabolic disorder.    -   G.15 Method G or G.1-G.4 wherein the condition to be treated or        controlled is cerebral edema consequent to glioma.    -   G.16 Method G or G.1-G.4 wherein the condition to be treated or        controlled is cerebral edema consequent to meningitis.    -   G.17 Method G or G.1-G.4 wherein the condition to be treated or        controlled is cerebral edema consequent to acute mountain        sickness.    -   G.18 Method G or G.1-G.4 wherein the condition to be treated or        controlled is cerebral edema consequent to water intoxication.    -   G.19 Method G or G.1-G.4 wherein the condition to be treated or        controlled is cerebral edema consequent to hepatic failure,        hepatic encephalopathy, or diabetic ketoacidosis.    -   G.20 Method G or G.1-G.3 wherein the condition to be treated or        controlled is cerebral edema consequent to an abscess.    -   G.21 Method G or G.1-G.3 wherein the condition to be treated or        controlled is cerebral edema consequent to eclampsia.    -   G.22 Method G or G.1-G.3 wherein the condition to be treated or        controlled is cerebral edema consequent to Creutzfeldt-Jakob        disease.    -   G.23 Method G or G.1-G.3 wherein the condition to be treated or        controlled is cerebral edema consequent to lupus cerebritis.    -   G.24 Method G or G.1-G.3 wherein the condition to be treated or        controlled is edema consequent to hypoxia, e.g., general        systemic hypoxia, e.g., hypoxia caused by an interruption of        blood perfusion, for example wherein the edema is cerebral edema        consequent to hypoxia caused by cardiac arrest, stroke, or other        interruption of blood perfusion to the brain, or wherein the        edema is cardiac edema consequent to cardiac ischemia or other        interruption of blood flow to the heart.    -   G.25 Method G or G.1-G.3 wherein the condition to be treated or        controlled is cerebral edema consequent to microgravity and/or        radiation exposure, e.g., exposure from space flight or from        working with radioactive materials or from working in        radioactive areas.    -   G.26 Method G or G.1-G.3 wherein the condition to be treated or        controlled is cerebral edema consequent to an invasive central        nervous system procedure, e.g., neurosurgery, endovascular clot        removal, spinal tap, aneurysm repair, or deep brain stimulation.    -   G.27 Method G.25 or G.26 wherein the patient is at elevated risk        of edema, e.g., due to microgravity and/or radiation exposure,        neurosurgery, endovascular clot removal, spinal tap, aneurysm        repair, or deep brain stimulation.    -   G.28 Method G.25 or G.26 wherein the patient already has edema.    -   G.29 Method G or G.1-G.28 wherein the edema is cytotoxic        cerebral edema or is primarily cytotoxic cerebral edema.    -   G.30 Method G, G.1-G.19, or G.24 wherein the edema is cytotoxic        cerebral edema or is primarily cytotoxic cerebral edema.    -   G.31 Method G, G.1, or G.2 wherein the condition to be treated        or controlled is spinal cord edema, e.g., spinal cord edema        consequent to a spinal cord trauma, e.g., spinal cord        compression.    -   G.32 Method G.31 wherein the condition to be treated or        controlled is spinal cord edema consequent to spinal cord        compression.    -   G.33 Method G, G.1, or G.2 wherein the condition to be treated        or controlled is optic nerve edema, e.g., optic nerve edema        consequent to microgravity and/or radiation exposure, e.g.,        exposure from space flight or from working with radioactive        materials or from working in radioactive areas.    -   G.34 Method G, G.1, or G.2 wherein the condition to be treated        or controlled is retinal edema.    -   G.35 Method G, G.1, or G.2 wherein the condition to be treated        or controlled is pulmonary edema.    -   G.36 Method G or G.1 wherein the condition to be treated or        controlled is epilepsy.    -   G.37 Method G or G.1 wherein the condition to be treated or        controlled is retinal ischemia or other diseases of the eye        associated with abnormalities in intraocular pressure and/or        tissue hydration.    -   G.38 Method G or G.1 wherein the condition to be treated or        controlled is myocardial ischemia.    -   G.39 Method G or G.1 wherein the condition to be treated or        controlled is myocardial ischemia/reperfusion injury.    -   G.40 Method G or G.1 wherein the condition to be treated or        controlled is myocardial infarction.    -   G.41 Method G or G.1 wherein the condition to be treated or        controlled is myocardial hypoxia.    -   G.42 Method G or G.1 wherein the condition to be treated or        controlled is congestive heart failure.    -   G.43 Method G or G.1 wherein the condition to be treated or        controlled is sepsis.    -   G.44 Method G or G.1 wherein the condition to be treated or        controlled is a migraine.    -   G.45 Method G or G.1 wherein the condition to be treated or        controlled is neuromyelitis optica.    -   G.46 Method G or G.1 wherein the condition to be treated or        controlled is glioblastoma.    -   G.47 Method G or G.1 wherein the condition to be treated or        controlled is fibromyalgia.    -   G.48 Method G or G.1 wherein the condition to be treated or        controlled is multiple sclerosis.    -   G.49 Method G wherein the aquaporin is AQP2.    -   G.50 Method G or G.49 wherein the condition to be treated or        controlled is hyponatremia or excessive fluid retention, e.g.,        consequent to heart failure (HF), for example congestive heart        failure, liver cirrhosis, nephrotic disorder, syndrome of        inappropriate antidiuretic hormone secretion (SIADH), or        infertility treatment.    -   G.51 Method G, G.49, or G.50 wherein the condition to be treated        or controlled is ovarian hyperstimulation syndrome.    -   G.52 Method G, G.49, or G.50 further comprising one or more of        restriction of dietary sodium, fluid and/or alcohol; and/or        administration of one or more diuretics, vasopressin receptor        antagonists, angiotensin converting enzyme (ACE) inhibitors,        aldosterone inhibitors, angiotensin receptor blockers (ARBs),        beta-adrenergic antagonists (beta-blockers), and/or digoxin.    -   G.53 Method G or G.1-G.52 wherein the pharmaceutical composition        comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered orally.    -   G.54 Method G or G.1-G.52 wherein the pharmaceutical composition        comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered parenterally.    -   G.55 Method G.54 wherein the pharmaceutical composition        comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered by injection, e.g.,        subcutaneously, intramuscularly, intravenously, or        intrathecally, e.g., a bolus injected subcutaneously,        intramuscularly, intravenously, or intrathecally.    -   G.56 Method G.55 wherein the pharmaceutical composition        comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered intravenously, e.g., IV        bolus and/or IV infusion, e.g., IV bolus followed by IV        infusion.    -   G.57 Method G or G.1-G.56 wherein the patient is human.    -   G.58 Method G or G.1-G.57 wherein the onset of action after        administration of the pharmaceutical composition comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is fairly rapid.

In yet another embodiment, provided is a method (Method H) of treatingor controlling a condition selected from fibromyalgia and multiplesclerosis comprising administering a pharmaceutical compositioncomprising 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyldihydrogen phosphate, e.g., Composition I, e.g., composition 1.1-1.124,to a patient in need thereof.

Further provided is Method H as follows:

-   -   H.1 Method H wherein the condition to be treated or controlled        is fibromyalgia.    -   H.2 Method H wherein the condition to be treated or controlled        is multiple sclerosis.    -   H.3 Method H, H.1, or H.2 wherein the pharmaceutical composition        comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered orally.    -   H.4 Method H, H.1, or H.2 wherein the pharmaceutical composition        comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered parenterally.    -   H.5 Method H.4 wherein the pharmaceutical composition comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered by injection, e.g.,        subcutaneously, intramuscularly, intravenously, or        intrathecally, e.g., a bolus injected subcutaneously,        intramuscularly, intravenously, or intrathecally.    -   H.6 Method H.5 wherein the pharmaceutical composition comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is administered intravenously, e.g., IV        bolus and/or IV infusion, e.g., IV bolus followed by IV        infusion.    -   H.7 Method H or H.1-H.6 wherein the patient is human.    -   H.8 Method H or H.1-H.7 wherein the onset of action after        administration of the pharmaceutical composition comprising        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate is fairly rapid.    -   H.9 Method H or H.1-H.8 wherein        2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl        dihydrogen phosphate binds to AQP4.

In yet another embodiment, provided is a pharmaceutical compositioncomprising 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyldihydrogen phosphate, e.g., Composition I, e.g., composition 1.1-1.124,for use in treating or controlling a disease or condition mediated by anaquaporin.

In yet another embodiment, provided is a pharmaceutical compositioncomprising 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyldihydrogen phosphate, e.g., Composition I, e.g., composition 1.1-1.124,for use in any of Methods A, e.g., A.1-A.58, any of Methods B, e.g.,B.1-B.41, any of Methods C, e.g., C.1-C.8, any of Methods D, e.g.,D.1-D.19, any of Methods E, e.g., E.1-E.59, any of Methods F, e.g.,F.1-F.5, any of Methods G, e.g., G.1-G.58, and any of Methods H, e.g.,H.1-H.9.

A dose or method of administration of the dose of the present disclosureis not particularly limited. Dosages employed in practicing the presentdisclosure will of course vary depending, e.g. on the particular diseaseor condition to be treated, the particular compound used, the mode ofadministration, and the therapy desired. The pharmaceutical compositionsmay be administered by any suitable route, including orally,parenterally, transdermally, or by inhalation. In stroke or otherseverely debilitating diseases or conditions, for example where thepatient may be unconscious or unable to swallow, an IV infusion and/orIV bolus may be preferred. In general, satisfactory results, e.g. forthe treatment of diseases as hereinbefore set forth are indicated to beobtained on oral administration at dosages of the order from about 0.01to 15.0 mg/kg. In larger mammals, for example humans, an indicated dailydosage for oral administration will accordingly be in the range of fromabout 0.75 to 1000 mg per day, conveniently administered once, or individed doses 2 to 3 times, daily or in sustained release form. Unitdosage forms for oral administration thus for example may comprise fromabout 0.2 to 75 mg or 150 mg, e.g. from about 0.2 or 2.0 mg to 50, 75,100, 125, 150 or 200 mg of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate together with a pharmaceutically acceptable diluent or carriertherefor. When the pharmaceutical composition is used via injection(subcutaneously, intramuscularly or intravenously) the dose may be 0.1or 0.25 mg to 500 mg per day, e.g., from about 0.25 mg to 75 or 150 mg,e.g., from about 0.1 or 0.25 or 2.0 mg to 50, 75, 100, 125, 150, 200,300, 400, or 500 mg, by bolus or if IV by bolus or infusion.

The pharmaceutical compositions as hereinbefore described for use in themethods of the invention may be used as a sole therapeutic agent, butmay also be used in combination or for co-administration with otheractive agents, for example in conjunction with conventional therapiesfor cerebral edema, stroke, traumatic brain injury, glioma (e.g.,glioblastoma), meningitis, acute mountain sickness, infection, metabolicdisorder, hypoxia, water intoxication, hepatic failure, hepaticencephalopathy, diabetic ketoacidosis, abscess, eclampsia,Creutzfeldt-Jakob disease, lupus cerebritis, optic nerve edema,hyponatremia, fluid retention, ovarian hyperstimulation syndrome,epilepsy, retinal ischemia or other diseases of the eye associated withabnormalities in intraocular pressure and/or tissue hydration,myocardial ischemia, myocardial ischemia/reperfusion injury, myocardialinfarction, myocardial hypoxia, congestive heart failure, sepsis,neuromyelitis optica, or migraines.

Further provided is crystalline2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate.

2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate includes its polymorphs, hydrates, solvates and complexes.

2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate may be made using the methods as described and exemplifiedherein and by methods similar thereto and by methods known in thechemical art. Such methods include, but not limited to, those describedbelow. If not commercially available, starting materials for theseprocesses may be made by procedures which are selected from the chemicalart using techniques which are similar or analogous to the synthesis ofknown compounds.

As used throughout, ranges are used as shorthand for describing each andevery value that is within the range. Any value within the range can beselected as the terminus of the range. In addition, all references citedherein are hereby incorporated by referenced in their entireties. In theevent of a conflict in a definition in the present disclosure and thatof a cited reference, the present disclosure controls.

Terms and Abbreviations

ala=alanine

Boc=tert-butyloxycarbonyl

DCC=dicyclohexylcarbodiimide

DMAP=4-(dimethylamino)pyridine

DMF=dimethylformamide

Hünig's base=N,N-diisopropylethylamine

TFA=trifluoroacetic acid

EXAMPLES Example 12-{[3,5-Bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate Step 1:N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide

5-chloro salicylic acid (8.75 g, 50 mmol, 1 eq) is dissolved in toluene(300 mL) under N₂ atmosphere then phosphorus trichloride (2.2 mL, 25mmol, 0.5 eq) is added dropwise followed by3,5-bis(trifluoromethyl)aniline (10 g, 43.7 mmol, 0.87 eq). The reactionmixture is stirred under reflux for 12 h then cooled to roomtemperature. The reaction mixture is quenched with NaHCO₃ saturatedsolution and stirred for 10 min. To this solution is added 1M HCl (100mL) until the pH of the aqueous layer is 5 and the aqueous layer isextracted with ethyl acetate (2×300 mL). The combined organics are thendried over sodium sulfate and concentrated in vacuo to yield the crudeproduct which is purified by flash chromatography (5-20% EtOAc/hex). Theyield of pure product as a white solid is 16 g (yield 85%) which is >95%pure by ¹H NMR. ¹H NMR (400 MHz, CDCl₃): δ 11.35 (bs, 1H), 10.85 (bs,1H), 8.40 (s, 2H), 7.80-7.79 (m, 2H), 7.50 (dd, 1H), 7.00 (d, 1H).

Step 2: 2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenylbis(2-(trimethylsilyl)ethyl) phosphate

N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide (4.0 g,0.01 mol, 1 eq) is dissolved in CH₃CN (104 mL) then DMAP (0.08 g, 0.001mol, 0.06 eq), Hunig's base (7.36 mL, 0.021 mol, 2 eq) and CCl₄ (8.02 g,0.052 mol, 5 eq) are added in this order. The solution is cooled to 0°C. and bis[2-(trimethylsilyl)ethyl] phosphonate (HP(O)(OCH₂CH₂Si(CH₃)₃)₂(4.66 g, 0.016 mol, 1.5 eq) in CH₃CN (5 mL) is added dropwise. Thereaction mixture is stirred at room temperature for 20 h then water isadded and extracted twice with EtOAc. The combined organic layers arewashed with a saturated solution of NaCl, dried over Na₂SO₄, filteredand the solvent is concentrated in vacuo to give the crude materialwhich is used as such for next step. ¹H NMR (200 MHz, CDCl₃): δ 10.20(bs, 1H), 8.32 (s, 2H), 7.90 (s, 1H), 7.62 (s, 1H), 7.45-7.40 (m, 1H),7.30-7.28 (m, 1H), 4.40-4.30 (m, 4H), 1.20-1.00 (m, 4H), 0.0 (s, 18H).

Step 3: 2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyldihydrogen phosphate

2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenylbis(2-(trimethylsilyl)ethyl) phosphate (6.64 g, 0.01 mol, 1 eq) isdissolved in a mixture TFA:Water (5:1, 50 mL). The reaction mixture isstirred at room temperature for 2 h then solvent is concentrated invacuo. The resulting white solid is dissolved in Et₂O (20 mL) thenconcentrated in vacuo. This operation is repeated twice or until thecompound becomes much less soluble in Et₂O. The resulting material issuspended in a mixture Et₂O:Hex (6:1, 50 mL) and filtered to give thedesire material as light red solid. Finally, the solid is dissolved inwater (100 mL), filtered and the resulting aqueous solution is freezedried to give the desired product as a white solid (yield 76% over twosteps, 97% pure by HPLC). ¹H NMR (400 MHz, CD₃OD): δ 8.38 (s, 2H), 7.78(s, 1H), 7.70 (s, 1H), 7.55-7.50 (m, 1H), 7.45-7.43 (m, 1H).

Example 2

A 95% pure lot of2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogenphosphate is purified as follows. 15 g is dissolved in 1.2 L of waterwith 120 mM of sodium hydroxide and extracted with 500 ml ethyl acetateto remove phenol and non acid impurities. The aqueous layer is acidifiedwith concentrated HCl to pH 1.2 and extracted with ethyl acetate 1 Lfollowed by 600 ml. The ethyl acetate layer is dried MgSO₄ and sodiumsulphate, filtered, and evaporated to give about 13 g of 98% pure2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogenphosphate. NMR showed 1 mole of ethyl acetate trapped in solid. Ethylacetate is removed by adding 100 ml of methanol and evaporating.2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogenphosphate is stable at RT for a week or more. Sample kept at RT. It issoluble at 5 mg/mL in 1% Na₂HPO₄ giving pH of about 7. Dissolved in 2%Na₂HPO₄ at 5 mg/mL gives pH of 7.4

Example 3

Mouse Water Toxicity Model—Survival Curves: The in vivo efficacies ofthe compounds are tested using the mouse water toxicity model, where amouse is injected with water at 20% of its body weight. Manley, G. T. etal. Aquaporin-4 deletion in mice reduces brain edema after acute waterintoxication and ischemic stroke. Nat Med 6, 159-163 (2000); Gullans, S.R. & Verbalis, J. G. Control of brain volume during hyperosmolar andhypoosmolar conditions. Annual Review of Medicine 44, 289-301 (1993).The resulting euvolemic hyponatremia rapidly leads to CE, making this apractical model to test an inhibitor of the CNS aquaporin, AQP4b.

The ability of mice to survive H₂O toxicity is determined in threeexperiments using 10-12 mice each (16-19 weak old male/female).Deionized water is prepared for injection with either 0.39 mg/kgphenylbenzamide (placebo) or 0.76 mg/kg with test compound. FIG. 1 showsthe combined results of these experiments (n=33 placebo, n=34N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide). Percentsurvival of theN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide cohortsimproves 3.2 fold and the time to 50% survival for animals treated withN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide isimproved by roughly 52 min.

Mouse Water Toxicity Model—Brain Volume by Magnetic Resonance Imaging(MRI): MRI is used to measure changes in brain volume in response towater shock, using the water toxicity model. As described for thesurvival and brain water content studies above, mice are injected, IP,with a water bolus alone or water bolus and test compound at 0.76 mg/kg,and changes in brain volume as detected by MRI are monitored. Mousebrain volumes are assessed using MRI scans collected with a 9.4T BrukerBiospec MRI scanner at the Case Center for Imaging Research at CaseWestern Reserve University. This imaging method is found to providesufficient contrast and resolution to sensitively detect changes intotal brain volume in the mouse water toxicity model for cerebral edema.High resolution T2-weighted sagittal scans (resolution=0.1 mm×0.1 mm×0.7mm) of the mouse head are obtained prior to water injection, 5.67 minpost water injection, and then every 5.2 minutes until the animalexpires from the water loading. Each scan contains twenty-five 0.7 mmcontiguous imaging slices of which 14-15 slices contain a portion of thebrain. The cross sectional area of the brain in each imaging slice ismeasured by manual region-of-interest selection using ImageJ. Brainvolumes are then calculated for each scan by summing the individualcross sectional brain areas and multiplying by the slice thickness (0.7mm).

Treatment withN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide(Compound 1) at 0.76 mg/kg reduces the rate of CE development from 0.081to 0.032 min⁻¹ (or 2.5-fold) fit to a single exponential model (FIG. 2).Also, the extent of CE during the period of observation is reduced (FIG.2). Moreover, plasma levels in the same assay are found to range between0.03-0.06 μg as determined by LC-MS/MS (performed at Lerner Center,Cleveland Clinic, Cleveland, Ohio) and are sufficient to show efficacyin this model for CE.

TABLE 1 Efficacy of compounds on CE formation in the mouse watertoxicity model AQP Inhibition Cerebral Edema Cell-Based Rate by MRICompound Assay (%) (min⁻¹) No Drug 0 0.081 N-[3,5- 47.9 0.032bis(trifluoromethyl)phenyl]-5- chloro-2-hydroxybenzamideFor no drug andN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide, n=14mice each.

Example 4—High Throughput Screening Assay

Under hypotonic shock, both untransfected cells and cells expressing anunrelated transmembrane protein (CD₈₁, at levels equivalent to AQP4b)swell slowly but remain intact. These observations are used to developour high-throughput screening assay (HTS).

After hypotonic shock in a 384 well plate format, we return osmolalityto normal (300 mOsm) by adding 2× concentrated phosphate buffered salinesupplemented to 2 μM with a nonfluorescent acetoxymethyl derivative ofcalcein (calcein-AM) to each well. Intact cells take up calcein-AM andconvert it to the fluorescent dye calcein—giving a quantitative measureof the remaining intact cells. Burst cells do not convert the precursorto the dye. Water uptake by AQP4-expressing cells is relatively rapid,with most test cells bursting within 4 min of hypotonic shock, whereasmost cells expressing CD81 remain viable after 8 min. Intracellularconversion of calcein-AM provides a strong and easily detectable signalat 535 nM in our assay (FIG. 3).

Calcein Fluorescence End-Point Assay:

Cells are seeded 24 hr before assay to reach 100% confluence. Culturemedium is replaced with H₂O for 5:30 min (osmotic shock). Osmolality isthen normalized with the addition of 2×PBS plus 2 μM calcein-AM. Cellsare then incubated at 37° C. for an additional 30 min and fluorescencemeasured on a plate-reader. Rows 1-22 are seeded with CHO-AQP4 cells,and rows 23-24, with CHO-CD81 cells (384 well plate). Note, all plateedges are discarded. Relative Fluorescence Intensity is calculated asthe fluorescence intensity (FI) of each well divided by the mean FI ofAQP4 cells treated with DMSO (control). Criteria for a successful assay:coefficients of variation (CVs)<15%, and Z-factors >0.5. Statisticalanalysis shows that 5.5 min of osmotic shock provides the optimalsignal-to-noise ratio.

TABLE 2 Statistics for endpoint ‘calccin’ assay in FIG. 3; 5:30 min timepoint shown: Mean StDev CV Z′ S/B AQP4 581618 66311 11% 0.629 5.0 CD812910106 221240 8%

As will be observed, the signal for the CD81 cells is ca. 5× higher thanthe signal for the APQ4 cells, because by 5.5 mins, most of the AQP4cells have burst, while most of the CD81 cells remain intact. Inhibitionof AQP4 would therefore be expected to provide a higher signal, morelike the CD81 cells.

This assay is applied in a pilot screen of the MicroSource GenPlus 960and the Maybridge Diversity™ 20 k libraries (approximately 21,000compounds tested, each compound at 10-20 μM).

From this assay, a specific chemical series is identified,phenylbenzamides, which represents 3 out of the top 234 hits.

Hits from the HTS are validated using the same assay using a differentplating arrangement. In FIG. 4, we show this validation assay used toexamine 5-chloro-N-(3,5-dichlorophenyl)-2-hydroxybenzamide. Cells areseeded in a 96 well multiplate format with the plates edges omitted(lanes 1 and 24) and an entire column (n=16) is used to test the abilityof a compound to block AQP4-mediated cell bursting upon H₂O shock. CHOcells expressing CD81 are seeded in lanes 2-3 as a control, and CHOcells expressing AQP4, in lanes 4-23. Cells are treated with 0.1% DMSOin 10% FBS, DMEM (even numbered columns) or 10 μMN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (oddnumber columns) in 0.1% DMSO, 10% FBS, DMEM for 30 minutes. The cellsare shocked with H₂O for 5:30 minutes, then osmolality returned to 300mOsm in the presence of 1 μM calcein-AM, as described above. The cellsare incubated at 37° C. for 30 minutes and the relative fluorescencemeasured (ex 495/em 535 nM) on a fluorescence multiplate reader. Thedata in FIG. 4 represents the average relative fluoresence units(RFU±SEM, n=16).

Example 5 Water Toxicity Model for CE: Intracranial Pressure (ICP)

ICP is monitored using a Samba 420 Sensor, pressure transducer, with aSamba 202 control unit (Harvard Apparatus, Holliston, Mass.). This ICPmonitoring system consists of a 0.42 mm silicon sensor element mountedon an optical fiber. A 20-gauge syringe needle is implanted through thecisterna magna to a depth of ˜1 cm. The needle then acts as a guide forinsertion of the Samba Sensor and the site of implantation and the openend of the needle are sealed with 100% silicone sealant. A baseline ICPreading is established followed by a water bolus IP injection (20%weight of animal) with or withoutN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide. ICP ismonitored until the animal expires from the water load.

Adjusting for the slight rise in ICP observed in the animals when theyare monitored without the water bolus injection (FIG. 5, No WaterToxicity),N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide(Compound 1) at 0.76 mg/kg reduces the relative rate of ICP rise by 36%,from 3.6×10⁻³ min⁻¹ to 2.3×10⁻³ min⁻¹ (n=6 mice/treatment, mean±SEM).

Example 5—Conversion from2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatebis ethanolamine salt toN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide

Plasma or serum levels of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate are measured by LC-MS/MS at the Mass Spectrometry II Corefacility at the Lerner Research Institute of the Cleveland ClinicFoundation. Measurements are taken at 15 minutes and 24 hours after a 10mg/kg i.p. loading dose and 1 mg/ml at 8 μl/h maintenance dose(delivered by an Alzet i.p. osmotic pump, Durect Corp., Cupertino,Calif.) of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenylphosphate bis ethanolamine salt (n=5 mice/time point, mean±SEM) (FIG.6). After initial processing to remove proteins (75% acetonitrileextraction), 5-chloro-N-(3,5-dichlorophenyl)-2-hydroxybenzamide isintroduced to improve quantitation using multiple reaction monitoring(MRM). Samples are analyzed by tandem LC-MS/MS using C18 reversed-phasechromatography and mass analysis with a triple-quadrapole massspectrometer. The LC method is sufficient to separateN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide(Compound 1) from 5-chloro-N-(3,5-dichlorophenyl)-2-hydroxybenzamide andsubsequent MRM gave reliable quantitation with a linear response from0.004-0.4 ng ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide(Compound 1) for its most abundant daughter ion. The dashed line in FIG.6 is the relative effective plasma concentration ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide(Compound 1) observed in the mouse water toxicity model. Inclusion of anAlzet osmotic pump (Durect Corp., Cupertino, Calif.) containing2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatebis ethanolamine salt in the peritoneum is sufficient, in conjunctionwith an initial loading dose, to sustainN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide(Compound 1) above the expected efficacious plasma concentration of 20ng/ml for 24 hours (FIG. 6).

The solubility ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide in wateris 3.8 μg/ml. The solubility of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatedisodium salt in water is 1 mg/ml.

Initial experiments show rapid bioconversion of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatebis ethanolamine salt toN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide whenadded to mouse plasma in vitro. Less than 5 minutes at 20° C. issufficient to render2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatebis ethanolamine salt undetectable. In addition,2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatebis ethanolamine salt is undetectable in plasma samples taken from miceinjected IP with2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatebis ethanolamine salt. Instead,N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide isdetected at a concentration consistent with good bioavailability andnear-complete conversion of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatebis ethanolamine salt. With2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatebis ethanolamine salt doses of 10 mg/kg and IP injection volumes insaline (0.5 ml for a 30 g mouse), that give serum concentrations ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide in excessof 400 ng/ml (FIG. 6) can be used. Key PK parameters in mice are: rateof absorption 0.12 min⁻¹; rate of elimination 0.017 min⁻¹.

Example 6—Animal Stroke Model

Most ischemic strokes (˜80%) occur in the region of the middle cerebralartery (MCA). To mimic this injury in mice, an intraluminal monofilamentmodel of middle cerebral artery occlusion (MCAo) is used. Occlusion isachieved by inserting a surgical filament into the external carotidartery (ECA) and threading it forward into the internal carotid artery(ICA) until the tip blocks the origin of the MCA. The resultingcessation of blood flow gives rise to subsequent brain infarction in theMCA territory (Longa, E. Z. et al., Reversible Middle Cerebral ArteryOcclusion Without Craniectomy in Rats, Stroke, 20, 84-91 (1989)). Thistechnique is used to study a temporary occlusion in which the MCA isblocked for one hour. The filament is then removed allowing reperfusionto occur for 24 hours before the animal's brain is imaged usingT2-weighted scans in a 9.4T Bruker MRI scanner at the Case Center forImaging Research (FIG. 7). FIG. 7 shows a single slice from aT2-weighted MR image depicting the center of the brain showing cerebralcortex, hippocampus, thalamus, amygdala and hypothalamus for a “Normal”mouse (left panels) and a mouse which receives MCAo for one hourfollowed by 24 hours of reperfusion (right panels). Dashed lines markthe midline of the brain and show a large shift in the MCAo brain due tocerebral edema. Solid line highlights the region of infarct in the MCAobrain.

Survival—

Mice are treated with2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatedisodium salt (Compound 5) using a 2 mg/kg i.p. loading dose and 1 mg/mlat 8 μl/h maintenance dose (delivered by an i.p. osmotic pump) of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatedisodium salt, or given saline (controls; n=17) using an identicalapproach. In this model, we observed a 29.4% improvement in overallsurvival at 24 h when animals are treated with2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatedisodium salt (X²(1)=4.26;P<0.05).

Cerebral Edema—

Mice are given saline or treated with2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatedisodium salt (Compound 5) by multi-dosing at 5 mg/kg i.p. every threehours (n=8 per treatment). This dosing regimen is sufficient to maintaina plasma concentration ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide >20 ng/mlfor the duration of the study. Ipsilateral and contralateral hemisphericvolume is measured from the T2-weighted MR images of mice 24 hourspost-icus. Relative change in hemispheric volume is calculated as apercent of the difference between ipsilateral brain volume (V_(i)) andcontralateral brain volume (Va) relative to the contralateral brainvolume (Percent Change in Hemispheric BrainVolume=((V_(i)−V_(c))/V_(c))×100%.

Control animals show swelling in the ipsilateral hemisphere with arelative change in ipsilateral brain volume of 13.4%±1.9%, while animalsgiven 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenylphosphate disodium salt (Compound 5) show a 4.2±1.7% change (P=0.003,±SEM, see FIG. 8). This represents a 3.2-fold reduction in brainswelling after MCAo.

Neurological Outcome—

In the same experiment as above, animals are scored for neurologicaloutcome on a simple 5 point scale described in Manley, G. T. et al.,Aquaporin-4 Deletion in Mice Reduces Brain Edema After Acute WaterIntoxication and Ischemic Stroke, Nature Medicine, 6, 159-163 (2000). Animprovement in neurological outcome is observed for animals given2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatedisodium salt (Compound 5). Control animals have an average neurologicalscore of 2.77±0.66, while animals given2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatedisodium salt (Compound 5) have an average score of 0.88±0.31 (FIG. 9,inset, P=0.025, n=9 per treatment). Animals given2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatedisodium salt (Compound 5) did not progress into a state of severeparalysis or death.

The data from the MCAo stroke model together with the water toxicity(brain edema) model link the pharmacology of2-{([3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphatedisodium salt (Compound5)/N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide(Compound 1) with improved outcomes in stroke.

Example 7 2-{[3,5-Bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyldihydrogen phosphate

Step 1: N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide

5-chloro salicylic acid (8.75 g, 50 mmol, 1 eq) is dissolved in toluene(300 mL) under N₂ atmosphere then phosphorus trichloride (2.2 mL, 25mmol, 0.5 eq) is added dropwise followed by aniline (10 g, 43.7 mmol,0.87 eq). The reaction mixture is stirred under reflux for 12 h thencooled to room temperature. The reaction mixture is quenched with NaHCO₃saturated solution and stirred for 10 min. To this solution is added 1MHCl (100 mL) until the pH of the aqueous layer is 5 and the aqueouslayer is extracted with ethyl acetate (2×300 mL). The combined organicsare then dried over sodium sulfate and concentrated in vacuo to yieldthe crude product which is purified by flash chromatography (5-20%EtOAc/hex). The yield of pure product as a white solid is 16 g (yield85%) which is >95% pure by ¹H NMR. ¹H NMR (400 MHz, CDCl₃): δ 11.35 (bs,1H), 10.85 (bs, 1H), 8.40 (s, 2H), 7.80-7.79 (m, 2H), 7.50 (dd, 1H),7.00 (d, 1H).

Step 2: 2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenylbis(2-(trimethylsilyl)ethyl) phosphate

N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide (4.0 g,0.01 mol, 1 eq) is dissolved in CH₃CN (104 mL) then DMAP (0.08 g, 0.001mol, 0.06 eq), Hunig's base (7.36 mL, 0.021 mol, 2 eq) and CCl₄ (8.02 g,0.052 mol, 5 eq) are added in this order. The solution is cooled to 0°C. and HP(O)(OCH₂CH₂Si(CH₃)₃)₂ (4.66 g, 0.016 mol, 1.5 eq) in CH₃CN (5mL) is added dropwise. The reaction mixture is stirred at roomtemperature for 20 h then water is added and extracted twice with EtOAc.The combined organic layers are washed with a saturated solution ofNaCl, dried over Na₂SO₄, filtered and the solvent is concentrated invacuo to give the crude material which is used as such for next step. ¹HNMR (200 MHz, CDCl₃): δ 10.20 (bs, 1H), 8.32 (s, 2H), 7.90 (s, 1H), 7.62(s, 1H), 7.45-7.40 (m, 1H), 7.30-7.28 (m, 1H), 4.40-4.30 (m, 4H),1.20-1.00 (m, 4H), 0.0 (s, 18H).

Step 3: 2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyldihydrogen phosphate

2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenylbis(2-(trimethylsilyl)ethyl) phosphate (6.64 g, 0.01 mol, 1 eq) isdissolved in a mixture TFA:Water (5:1, 50 mL). The reaction mixture isstirred at room temperature for 2 h then solvent is concentrated invacuo. The resulting white solid is dissolved in Et₂O (20 mL) thenconcentrated in vacuo. This operation is repeated twice or until thecompound becomes much less soluble in Et₂O. The resulting material issuspended in a mixture Et₂O:Hex (6:1, 50 mL) and filtered to give thedesire material as light red solid. Finally, the solid is dissolved inwater (100 mL), filtered and the resulting aqueous solution is freezedried to give the desired product as a white solid (yield 76% over twosteps, 97% pure by HPLC). ¹H NMR (400 MHz, CD3OD): δ 8.38 (s, 2H), 7.78(s, 1H), 7.70 (s, 1H), 7.55-7.50 (m, 1H), 7.45-7.43 (m, 1H).

Example 8 2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenylphosphate bis ethanolamine salt

2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogenphosphate (2.14 g, 0.005 mol, 1 eq) is dissolved in MeOH (46 mL) thenethanolamine (0.56 mL, 0.009 mol, 2 eq) is added. The reaction mixtureis stirred at room temperature for 2 h then solvent is concentrated invacuo to give the desired product as a white solid (yield 84%, 97% pureby HPLC). ¹H NMR (300 MHz, D₂O): δ 8.15 (s, 2H), 7.85 (d, 2H), 7.37-7.34(m, 2H), 3.62 (t, 4H), 2.95 (t, 4H).

Example 9 2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenylphosphate bis diethanolamine salt

2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogenphosphate (300 mg, 0.647 mmol, 1 eq) is dissolved in MeOH (3.2 mL) thendiethanolamine (0.124 mL, 1.294 mmol, 2 eq) is added. The reactionmixture is stirred at room temperature for 2 h then solvent isconcentrated in vacuo to give the desire product as a yellow foam (yield100%, 95% pure by HPLC). ¹H NMR (500 MHz, DMSO-d₆): δ 8.52 (s, 2H), 7.76(s, 1H), 7.62 (s, 1H), 7.48 (d, 1H), 7.37 (d, 1H), 3.55 (s, 8H), 2.80(s, 8H).

Example 10 2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenylphosphate bis triethanolamine salt

2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogenphosphate (300 mg, 0.647 mmol, 1 eq) is dissolved in MeOH (3.2 mL) thentriethanolamine (0.172 mL, 1.294 mmol, 2 eq) is added. The reactionmixture is stirred at room temperature for 2 h then solvent isconcentrated in vacuo to give the desired product as a yellow oil (yield100%, 98% pure by HPLC). ¹H NMR (500 MHz, DMSO-d₆): δ 8.50 (s, 2H), 7.76(s, 1H), 7.62 (s, 1H), 7.52 (d, 1H), 7.29 (d, 1H), 3.55 (s, 12H), 2.82(s, 12H).

Example 11 2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenylphosphate bis sodium salt (Compound 5)

2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogenphosphate (300 mg, 0.647 mmol, 1 eq) is suspended in water (6.4 mL) thenNaOH (1M) (1.29 mL, 1.294 mmol, 2 eq) is added. The reaction mixture isstirred at room temperature for 2 h then the solution is filtered andfreeze dried to give the desired product as a white solid (yield 100%,93% pure by HPLC).

Example 12 2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenylphosphate bis potassium salt

2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogenphosphate (300 mg, 0.647 mmol, 1 eq) is suspended in water (6.4 mL) thenKOH (1M) (1.29 mL, 1.294 mmol, 2 eq) is added. The reaction mixture isstirred at room temperature for 2 h then the solution is filtered andfreeze dried to give the desired product as a white solid (yield 100%,82% pure by HPLC).

Example 13 2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenylhydrogen phosphate mono sodium salt,2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl phosphatebis sodium salt, and2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl phosphatebis ethanolamine salt

2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl hydrogenphosphate mono sodium salt,2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl phosphatebis sodium salt, and2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl phosphatebis ethanolamine salt are made as follows: 2 mM of2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogenphosphate is dissolved in ethanol 50 ml and appropriate equivalents ofeach base are added. Evaporation gives salts which are dissolved inwater and freeze dried.

Example 14 2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenylhydrogen phosphate mono ethanolamine salt

2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl hydrogenphosphate mono ethanolamine salt is made as follows: 1 g of2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogenphosphate is dissolved in isopropanol and 1 eq ethanol amine is added.Evaporation gave2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl hydrogenphosphate mono ethanolamine salt.

Example 15

Stability and Solubility

To understand the stability and solubility of the novel prodrug salts a95% pure lot of2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogenphosphate is purified as follows. 15 g is dissolved in 1.2 L of waterwith 120 mM of sodium hydroxide and extracted with 500 ml ethyl acetateto remove phenol and non acid impurities. The aqueous layer is acidifiedwith concentrated HCl to pH 1.2 and extracted with ethyl acetate 1 Lfollowed by 600 ml. The ethyl acetate layer is dried MgSO₄ and sodiumsulphate, filtered, and evaporated to give about 13 g of 98% pure2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogenphosphate. NMR showed 1 mole of ethyl acetate trapped in solid. Ethylacetate is removed by adding 100 ml of methanol and evaporating.2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogenphosphate is stable at RT for a week or more. Sample kept at RT. It issoluble at 5 mg/mL in 1% Na₂HPO₄ giving pH of about 7. Dissolved in 2%Na₂HPO₄ at 5 mg/mL gives pH of 7.4

2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl hydrogenphosphate mono sodium salt (“mono sodium salt”),2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl phosphatebis sodium salt (“bis sodium salt”), and2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl phosphatebis ethanolamine salt (“bis ethanolamine salt”) are made and freezedried as in Example 13. In all cases stability studies show hydrolysisin the solid state at about 1% per day. Solubilities are about 5 mg/mLfor mono sodium salt and 10 mg/mL for both bis sodium and bisethanolamine salt in water.

Final pH of solutions are about 7.5 for the bis ethanolamine salt, pH8.5 for mono sodium salt, and pH 9.5 for bis sodium salt in water. Inall cases solutions of these salts show less than 1% phenol over 12 hrs.Longer term their stability is the same as the solid samples (about 1%per day at RT). Hydrolysis rate is expected to be faster at higher pH.

2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl hydrogenphosphate mono ethanolamine salt (“mono ethanolamine salt”) is made asin Example 14. Surprisingly, the mono ethanolamine salt only shows about1% hydrolysis after 5 days at RT. Its solubility in water is about 5mg/ml. Solubility is expected to be higher at higher pH.

Example 16 Synthesis of Ala and Ala Ala Prodrugs ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide

To 750 mg ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (2 mM) in10 ml of DMF was added 360 mg (2 mM) of boc ala followed by 400 mg DCC(2 mM). Reaction is stirred for 3 hrs. and then filtered. To DMF isadded 200 ml water and extracted with ethyl acetate. Extract is driedand evaporated. Purified on combi flash hexane to 50% ethyl acetate.Yield 800 mg of Compound 11 wherein R²=Boc.

To 800 mg Compound 11 wherein R²=Boc in 6 ml THF is added 3 ml of 4N HClin dioxane and stirred overnight. Product precipitates. 30 ml ether isadded and product is filtered off, washed with ether, and dried to give500 mg of Compound 12 as an HCl salt as a white powder.

Compound 12 wherein R² is CH₃C(O)CH(CH₃)NHBoc is synthesized using thesame method but when tried to filter off, solid it turned into an oil.Ether is added and decanted several times. Finally compound solidifies.The solid is sticky and hygroscopic. Yield is about 100 mg.

Solubility

Both prodrugs are insoluble in water and pH 7.4 water even afterstirring for 4-5 hrs., as determined by HPLC analysis of filtrate.

Example 17-2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyldihydrogen phosphate (Formula I) and tris(hydroxymethyl)aminomethane

2.5 to 5 equivalents of tris(hydroxymethyl)aminomethane is added to2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate (Formula I). Water is added and the mixture is stirred orsonicated. Yields 10 mg/ml to 20 mg/ml solutions stable for at least 24hrs.

HPLC conditions for assaying the stability of compositions formed from2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate and a base, e.g., tris(hydroxymethyl)aminomethane are asfollows:

-   -   Hplc condition c18 SB Agilent 4.6×125 mm column 3 or 5 u    -   At 1.5 ml per min 10% to 100% acetonitrile with 2 g ammonium        acetate per 4 l of water    -   Using waters 2695 hplc running millennium 32 software    -   No baseline subtraction

Solid state compositions of the invention falling under Composition Ishow about 1% ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide over afour month period at room temperature as measured under the HPLCconditions above.

Reconstituted compositions of the invention falling under Composition Ishow 1-2% degradation over a 24 hour period.

Example 18—Conversion from2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl phosphateTris-Base solution toN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide

The 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyldihydrogen phosphate is dissolved at 10 mg/mL in 0.07% aqueousTris-Base. This solution is then diluted to 5 mg/ml with water and usedto fill an Alzet osmotic pump (DURECT, Corp., model 2001D, delivery at 8ul/hr for 24 hrs). Surgery is performed on an anesthetized mouse understerile conditions to implant the pump in the peritoneal cavity. Oncethe abdominal incision is closed with sutures, muscle layer followed byskin, an IP bolus of 10 mg/kg is given. For this bolus the 10 mg/mL2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate solution is diluted to 1 mg/ml with water and the appropriatevolume administered. At 15 min, 6 hr, 18 hr and 24 hr post injectionblood is drawn by tail laceration, serum prepared and stored at −20 Cfor later processing. In preparation for LC-MS/MS, an aliquot of theserum sample is diluted 4-fold with acetonitrile to precipitate proteinsand ensure soluble release of the parent compoundN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide. Theprotein is removed by centrifugation and the supernatant diluted to37.5% acetonitrile using water.5-chloro-N-(3,5-dichlorophenyl)-2-hydroxybenzamide is added as aninternal standard and the sample run on LC-MS/MS. In this experimentn=3. See FIG. 10. The dashed line in FIG. 10 is the relative effectiveplasma concentration ofN-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide(Compound 1) observed in the mouse water toxicity model.

The invention claimed is:
 1. A pharmaceutical composition comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate (Formula I)

and one or more Bronsted bases, wherein the one or more Bronsted basesis a solid, and wherein the pharmaceutical composition has <2%N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide after oneweek at room temperature, and the pharmaceutical composition is suitablefor dissolution with an aqueous solution to form an injection.
 2. Amethod of making the pharmaceutical composition of claim 1 comprisingadmixing 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyldihydrogen phosphate and one or more Bronsted bases.
 3. A kit, whereinthe kit comprises one or more containers comprising2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate (Formula I)

and one or more Bronsted bases, wherein the kit has <5%N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide after oneweek at room temperature.
 4. The kit of claim 3, wherein a conjugateacid of the one or more Bronsted bases has a pKa between 6 and
 11. 5.The kit of claim 3, wherein a conjugate acid of the one or more Bronstedbases has a pKa between 8 and
 10. 6. The kit of claim 3, wherein the oneor more Bronsted bases are selected from the group consisting of aC₁₋₈-alkyl mono-, di-, or tri-carboxylic acid salt, a phosphate salt, anamine, an amine salt, an acetate salt, a hydroxide salt, an alkoxidesalt, a carbonate salt, a bicarbonate salt, and a metal borate salt. 7.The kit of claim 3, wherein the one or more Bronsted bases are an amineand/or a salt thereof.
 8. The kit of claim 7, wherein the one or moreBronsted bases are (HO)_(n)R⁸NH₂, [(HO)_(n)R⁸]₂NH, [(HO)_(n)R⁸]₃N,and/or a salt thereof, wherein each R⁸ is independently C₁₋₈ alkyl and nis 0 or C₁₋₈-alkylene and each n is independently 1-8.
 9. The kit ofclaim 3, wherein the one or more Bronsted bases aretris(hydroxymethyl)aminomethane, meglumine, ethanolamine and/or atris(hydroxymethyl)aminomethane salt.
 10. The kit of claim 3, whereinthe one or more Bronsted bases are an alkali carbonate salt and/or asodium phosphate.
 11. The kit of claim 3, wherein Formula I islyophilized.
 12. The kit of claim 3, wherein Formula I is amorphous. 13.The kit of claim 3, wherein Formula I and the one or more Bronsted basesare in the same container.
 14. The kit of claim 3, wherein the one ormore Bronsted bases is a solid.
 15. The kit of claim 3, wherein the kitfurther comprises an aqueous solution for mixture with Formula I to forman injection.
 16. The kit of claim 15, wherein the aqueous solution issterile water for injection, a sterile solution comprising dextrose, asterile solution comprising sodium chloride, a sterile solutioncomprising benzyl alcohol, or Lactated Ringer's.
 17. The kit of claim16, wherein the aqueous solution is sterile water for injection or 0.9%sodium chloride injection.
 18. The kit of claim 15, wherein Formula I isin a first container and the one or more Bronsted bases are dissolved inthe aqueous solution in a second container.
 19. The kit of claim 3,wherein the kit has <2%N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide after oneweek at room temperature.
 20. The kit of claim 18, wherein the kit has<2% N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide afterone week at room temperature.
 21. The kit of claim 3, wherein the kitcomprises instructions for administering Formula I to a patient in needthereof.
 22. The kit of claim 21, wherein the kit comprises instructionsfor administering Formula I to a patient in need thereof to treat edema.23. The kit of claim 22, wherein the edema is cerebral edema.
 24. Thekit of claim 23, wherein the cerebral edema is consequent to an ischemicstroke, traumatic brain injury, or closed head trauma.
 25. The kit ofclaim 23, wherein the cerebral edema is consequent to an ischemicstroke.
 26. The kit of claim 24, wherein the cerebral edema is cytotoxiccerebral edema.
 27. The kit of claim 25, wherein the cerebral edema iscytotoxic cerebral edema.
 28. A method of administering apharmaceutically acceptable salt of2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogenphosphate (Formula I)

by injection to a human, wherein the method comprises mixing Formula I,one or more Bronsted bases, and an aqueous solution to form acomposition and administering the composition thus obtained 24 hours orless after mixture with the aqueous solution to the human.
 29. Themethod of claim 28, wherein the human has cerebral edema.
 30. The methodof claim 29, wherein the cerebral edema is consequent to a stroke,traumatic brain injury, closed head trauma, or hypoxia.
 31. The methodof claim 29, wherein the cerebral edema is consequent to an ischemicstroke.
 32. The method of claim 30, wherein the hypoxia is caused bycardiac arrest, stroke, or other interruption of blood perfusion to thebrain.
 33. The method of claim 30, wherein the cerebral edema iscytotoxic cerebral edema.
 34. The method of 31, wherein the cerebraledema is cytotoxic cerebral edema.